人类LRP5基因和KLF15基因的转录调控机制研究
摘要
第一部分人类LRR5基因的转录调控机制研究
低密度脂蛋白受体相关蛋白5基因(low-density lipoprotein receptor related protein 5, LRP5)定位于人类染色体11q13,有23个外显子,编码一个属于低密度脂蛋白受体超家族的含有1615个氨基酸的单个跨膜受体蛋白。LRP5在成人和胚胎组织中广泛表达,其中肝脏表达最高。在骨骼组织中,LRP5主要在骨内膜和小梁骨表面的成骨细胞中表达,而不在破骨细胞中表达。
LRP5在胚胎发育过程中调节多个发育过程,在个体成熟过程中也起着维持生理平衡作用。LRP5基因缺失功能突变导致骨质疏松,而获得功能突变导致骨密度升高,表明LRP5基因在骨形成中发挥着重要的作用,这种作用主要是通过Wnt信号传导通路来完成的。此外,LRP5在血管形成或再生以及正常的脂质代谢和糖代谢中也发挥重要作用。
尽管对LRP5的功能进行了大量研究,但LRP5基因的表达调控机制目前仍不清楚。为此,我们对LRP5基因的表达调控机制进行了分析,取得了以下结果：
1.确定了LRP5基因转录起始点：采用引物延伸方法,我们分析了LRP5基因转录起始点,发现人类LRP5基因的转录起始点位于翻译起始点上游114bp处,距离LRP5基因cDNA序列NM_002335的5′末端40bp处。
2.为寻找LRP5基因转录起始点上游顺式调控元件,我们采用MatInspector和AliBaba 2.1分析软件对LRP5基因翻译起始点上游2495bp片段进行了分析,发现该DNA片段缺乏经典的TATA盒和CAAT盒,但是含有多个可以与Sp1结合的GC盒,以及KLF15,CDE,MAZ,ZBPF等转录因子结合位点。利用荧光素酶报告基因系统,我们分析了该基因组片段在U20S细胞和HEK293细胞中的转录活性,发现该片段具有启动子活性。
3.为了定位启动子核心区域,我们构建了系列截短载体pWT-2015, pWT-1594, pWT-1442, pWT-1309, pWT-1167, pWT-1085, pWT-953, pWT-359, pWT-219, pWT-167, pWT-72, pWT-53和pWT-40,瞬时转染U20S细胞和HEK293细胞并测定荧光素酶活性,结果表明载体在两种细胞中的转录活性趋势一致,提示这些区域内不含有组织特异性调控元件。对比分析不同截短载体表达活性发现人类LRP5基因的基本启动子位于-72至-53之间。
4.软件分析发现在-72至-53之间存在一个KLF15识别结合位点和一个Spl识别结合位点,且两个位点部分重叠。为确定二者在LRP5基因转录调控中的作用,我们构建了两个位点单突变和双突变表达载体,荧光素酶活性分析表明KLF15结合位点和Sp1结合位点是决定LRP5基因基本启动子活性所必需的。
5. EMSA分析发现,包含-72至-53区域的野生型探针能特异性地结合核蛋白,非标记的野生型探针能有效竞争标记探针与核蛋白形成复合物,而非标记的突变型探针则无明显竞争作用,说明该区域的KLF15和Sp1结合位点能特异性结合核蛋白。利用抗Sp1抗体和抗KLF15抗体进行ChIP分析,发现在两个抗体沉淀的染色质复合物中能检测到-72至-53区域DNA片段,进一步证实该区域能特异性与KLF15和Sp1结合。
6.在缺乏KLF15和Sp1蛋白的Drosophila SL2细胞株中共转染pPac-KLF15或者pPac-Sp1表达载体,发现Sp1或KLF15增加LRP5基因启动子活性依赖于LRP5基因-72至-53bp区相应结合位点的存在。
以上研究从Sp1和KLF15结合序列到转录因子以及转录因子与结合位点结合等方面证实LRP5基因-72bp-53bp区域内的Sp1和KLF15结合位点是人LRP5基因启动子功能的所需要的。
第二部分KLF15调节内源性LRR5基因表达
KLF15属于锌指蛋白转录因子家族,既具有转录激活作用,又具有转录抑制作用。本文第一部分利用报告基因分析方法发现,KLF15和Spl共同激活LRP5基因转录。为进一步证实KLF15在生理状态下也可调控LRP5基因转录,本部分以C2C12细胞株为研究对象,该细胞株属于小鼠骨骼肌成肌细胞系,具有多种分化潜能。可以在不同条件诱导下分化为肌管、脂肪细胞和成骨细胞。采用适时定量PCR和Western blotting分析不同诱导分化条件下KLF15表达情况及其对LRP5的转录调控作用,取得了以下结果：
1.用含有2%马血清的DMEM培养基能诱导C2C12细胞分化为肌管,可以观察到细胞形态由典型的梭形和多角形的成纤维样细胞分化为呈平行排列走向,相互融合形成中央核的多核性长管状初生肌管；实时定量PCR检测到肌管的标志基因myogenin表达明显上调。在C2C12诱导分化为肌管过程中,KLF15的mRNA和蛋白质表达水平明显增高,LRP5 mRNA表达水平也明显增加。
2.用5μM的罗格列酮生长培养基能诱导C2C12细胞分化为脂肪细胞,油红0染色可以观察到明显的脂肪细胞产生的脂滴；实时定量PCR检测到脂肪细胞标志基因aP2表达明显上调。在C2C12向脂肪细胞分化过程中,KLF15的mRNA和蛋白质表达水平明显增高,LRP5 mRNA表达水平也明显增加。
3.用成骨培养基能诱导C2C12细胞分化为成骨细胞,茜素红染色可以观察到骨结节形成；实时定量PCR检测到成骨细胞标志基因ALP表达明显上调。在C2C12向成骨细胞分化过程中,KLF15的mRNA和蛋白质表达水平均明显增高,LRP5mRNA表达水平也明显增加。
通过分析C2C12细胞诱导分化为肌管、脂肪细胞和成骨细胞过程中KLF15和LRP5的表达变化,进一步证实LRP5是KLF15转录因子的靶基因,KLF15可以激活LRP5基因转录。
第三部分人类KLF15基因的转录调控机制研究
如前所述,KLF15可以激活基因转录,也可以抑制某些基因转录。前两部分结果均显示KLF15可以在多种细胞分化过程中上调并激活LRP5基因转录。但是到目前为止,对KLF15的转录调控机制尚不明确。为此,本部分对KLF15基因的转录调控机制进行了分析。
1.采用MatInspector和AliBaba 2.1网上软件对KLF15基因启动子区域序列进行分析,发现KLF15启动子缺乏经典的TATA盒,但是富含可以结合Sp1的GC盒子,同时也含有USF1、Smad 4、AP2、CREB、Smad3和NFY等识别结合位点。
2.采用荧光素酶报告基因分析系统,我们构建了序列截短荧光素酶报告基因表达载体pGL3-1804, pGL3-1505, pGL3-863, pGL3-792, pGL3-514, pGL3-217,pGL3-189, pGL3-80, pGL3-45和pGL3-5,瞬时转染HEK293细胞后测定荧光素酶活性。分析这些表达载体荧光素酶表达活性发现人类KLF15基因的转录调控关键元件位于转录起始点上游-189至-80和-80至-45之间的两个区域。
3.软件分析发现-189至-80区域内含有四个GC盒,分别命名为GC1、GC2、GC3和GC4。突变分析发现,GC2和GC3起主要作用,GCl位点作用较小,但在GC2或GC3突变后GC1可能发挥替代作用。
4.在-80至-45之间存在一个E-box保守序列和一个CREB识别结合位点,且两个位点部分重叠。缺失和突变分析发现,E-box是维持人类KLF15基因启动子活性所必需的。利用RNA干扰CREB基因实验排除了该区域CREB识别结合位点的作用。
5. EMSA分析证明-189至-155区域内的GC盒序列可以与核蛋白形成特异性DNA蛋白质复合物,未标记的野生型探针能有效竞争复合物形成,而未标记的突变型探针不影响复合物形成。ChIP分析也证实该区域序列能特异性与Spl蛋白结合。
6. EMSA分析证明-80至-45区域内的E-BOX能与核蛋白结合形成特异性DNA蛋白质复合物,未标记的野生型探针能有效竞争复合物形成,而未标记突变探针不影响复合物形成。ChIP实验进一步证实该区域可以特异性与转录因子USF1结合。
综上所述,本研究采用缺失和突变分析、EMSA、ChIP分析等方法证实USF1和SP1通过分别与KLF15基因启动子近侧-80至-45区域内的E-box和-189至-155区域的GC-box结合调节KLF15基因转录。
Part 1. Regulation of human LRP5 gene transcription
LRP5 (low-density lipoprotein receptor related protein 5), located on human chromosome 11ql3, contains 23 exons encoding a 1615 amino acid single-pass transmembrane receptor that belongs to the low density lipoprotein (LDL) receptor superfamily. LRP5 is expressed in multiple adult and embryonic tissues with strongest expression occurring in the live. In bone, it is expressed by osteoblasts of the endosteal and trabecular bone surfaces but not osteoclasts.
LRP5 regulates diverse developmental processes in embryogenesis and maintains physiological homeostasis in maturity. Loss-of-function mutation in LRP5 can result in osteoporosis, and gain-of-function mutation leads to high bone mass (HBM), indicating that LRP5 plays an important role in bone formation. Such role is through the Wnt signaling pathway. In addition to these roles, the LRP5 is also required for normal cholesterol and glucose metabolism.
Despite lots of effort has been done in study of function of LRP5, the molecular regulation of LRP5 expression remains unclear. Therefore, we studied the transcriptional regulation of LRP5 and got the following results:
1. Determination of the transcriptional start site of LRP5 gene. Using primer extension, we identified the transcriptional start site of LRP5 gene, and found that the transcriptional start site is located at the 114bp upstream of the translational start site,40 nucleotides upstream of the 5'end of the published cDNA sequence (GenBank accession no. NM002335).
2. In order to identify putative transcriptional factor binding sites, we analyzed a 2495bp region upstream of translational start site of LRP5 using the programs Matlnspector (www.genomatix.de/products/MatInspector/) and AliBaba 2.1 (www.gene-regulation.com/pub/programs.html), and failed to find any canonical TATA box or CAAT-like sequence. However, several potential transcription factor binding motifs were identified in the promoter region close to transcription start site, including Sp1, KLF15, CDE, MAZ, and ZBPF. Using luciferase reporter gene, we tested the transcriptional activity of this fragment in U2OS cells and HEK293 cells, and found this region has promoter activity.
3. To determine the minimal region required for basal activity of the promoter, a series of deletion constructs were generated and designated as pWT-2015, pWT-1594, pWT-1442, pWT-1309, pWT-1167, pWT-1085, pWT-953, pWT-359, pWT-219, pWT-72, pWT-53 and pWT-40 based on their variable 5'end. These constructs were tested for their ability to drive the luciferase reporter gene in transiently transfected U2OS and HEK293 cells. Similar trends were observed in these two cell lines, suggesting that cell-specific element may not be present in those sequences. Comparing the expression activity of different deletion constructs, the proximal promoter has been located at-72 and-53.
4. With software analysis, two overlapped transcriptional factor binding sites, one for KLF15 and the other for Sp1, were found in-72 to-53. To determine the contribution of the Spl and/or KLF15 sites to the promoter activity, constructs with either single or double mutant reporters were generated. The luciferase activity assay showed both KLF15 and Spl binding sites between-72 and-53 of human LRP5 promoter contributes to the basal activity of human LRP5 transcription.
5. It is found in EMSA that wild type probe containing the region-72 to-53 can specificly binds to nuclear proteins. Unlabeled wild type probe can effectively abolish the complex of labeled probe and nuclear protein, while unlabeled mutant probe can't, indicating that the KLF15 and Spl sites can specificly bind to nuclear proteins. In ChIP analysis using anti-Sp1 and anti-KLF15 antibodies, DNA fragment from-72 to-53 can be detected from co-immunoprecipitated chromatin complex. This result further confirmed this region can specificly bind to KLF15 and Sp1.
6. By co-transfecting Drosophila SL2 cells lacking KLF15 and Spl proteins with pPac-KLF15 and pPac-Spl, it is found that the increase of LRP5 promoter activity by Spl or KLF15 relies on the existence of corresponding binding sites in-72 to-53.
The foregoing study from different aspects, including the binding sites of Spl and KLF15, transcription factor and their binding, proved the Spl and KLF15 binding sites in-72 to-53 of LRP5 gene are essential for its promoter activity.
Part 2. KLF15 regulates the transcription of endogenous LRP5
Kruppel-like factors (KLFs), a subclass of the zinc-finger family of transcriptional regulators, can function as transcriptional activators and/or repressors depending on promoter context. In the first part, we demonstrated that both KLF15 and Sp1 functions as a positive regulatory element and activates the human LRP5 promoter. C2C12 cell line, a muscle satellite cell line, can differentiate into myotubes, adipocytes and osteoblasts under different condition. Using quantitative PCR and Western blotting, the expression of KLF15 and its regulation of transcription of LRP5 under different differentiating condition were detected, and the results are as following.
1. C2C12 cell matained in DMEM medium with 2% horse serum was induced to the typical morphology of multinucleated myotube. Myotube-specific myogenin gene was dramaticlly upregulated during myogenic differentiation as determined by real-time PCR. During myogenic differentiation, both mRNA and protein of KLF15 were significantly increased. Consequently, LRP5 transcription was significantly upregulated.
2. C2C12 cells matained in the adipogenic medium containg 5μM rosiglitazone became adipose-like morphology and contain lipid droplet which can be stained with Oil red O. The successful induction was confirmed by the significant upregulation of aP2 mRNA, an adipose-sepcific marker, during the adipogenic differentiation. The KLF15 expression was significantly upregulated at both mRNA and protein levels. LRP5 mRNA level was also increased during the adipogenic differentiation.
3. C2C12 matained in osteogenic differentiation medium was induced to differentiate toward osteoblast. On day 24 after treatment, the mineralized nodules were detected by Alizarin red staining. The ALP mRNA, osteoblast-specific gene, was upregulated during the differentiation process. Both mRNA and protein levels of KLF15 gene were significantly induced during differentiation. Consequently, LRP5 mRNA was significantly upregulated.
Taken together, inducing C2C12 cells to differentiate toward myogenis, adipogenis and osteogenis can alter the expression of KLF15 and LRP5. These further confirmed that LRP5 is the target gene of KLF15 and KLF15 can activate the transcription of LRP5 gene.
Part 3. Regulation of human KLF15 gene transcription
KLF15 can activate, as well as repress, gene transcription. The results of last two parts all showed KLF15 can be upregulated during cell differentiation and activate the transcription of LRP5 gene. However, the regulation of transcription of KLF15 is still unknown. Therefore, in this part we studied the regulation mechanism of KLF15 transcription.
1. Using the programs MatInspector (www.genomatix.de/products/MatInspector/) and AliBaba 2.1 (www.gene-regulation.com/pub/programs.html) to analyze the promoter sequence of KLF15 gene, we failed to find any canonical TATA box. However, multiple potential transcription factor binding motifs were identified, including five GC-boxes that can bind to Spl, as well as USF1, CREB, Smad3, Smad4, AP2, and NYF sites.
2. Serial deletion constructs with luciferase reporter gene, pGL3-1804, pGL3-1505, pGL3-863, pGL3-792, pGL3-514, pGL3-217, pGL3-189, pGL3-80, pGL3-45 and pGL3-5, were generated, and luciferase activity were measured after transient transfecting these constructs into HEK293 cells. According to the luciferase activity of these deletion constructs, it is found that the proximal transcription regulator is located in-189 to-80 and-80 to-45.
3. Four GC boxes, designated as GC1, GC2, GC3 and GC4, were found within-189 to-80 by software analysis. Through site-direct mutagenesis, we found GC2 and GC3 play an important role in regulation of KLF15 transcription. The effect of GC1 is not so strong, but might become important after GC2 or GC3 mutated.
4. There are two partially overlapping sites, one E-box consensus sequence and one CREB binding sits within-80 to-45. After deletion and mutation, E-box was found as an essential element that maintains the promoter activity of human KLF15 gene. The possibility of effect of CREB on promoter activity was excluded using RNA interference of CREB.
5. EMSA results showed that GC boxs located in-189 to-155 can form specific DNA-protein complex with nuclear protein. Unlabeled wild type probe can effectively abolish this complex, whereas the unlabeled mutant probe can't. ChIP results also confirmed that Spl protein can specificly bind to this region.
6. Also with EMSA was E-Box found to be able to form specific DNA-protein complex. Unlabeled wild type probe can effectively abolish this complex, whereas the unlabeled mutant probe can't. ChIP results also confirmed that transcription factor USF1 can specificly bind to this region.
In summary, this study adopting different approaches, such as deletion and mutation analysis, EMSA, ChIP, to prove that USF1 and Spl can bind to E-box in-80 to-45 and GC-box in-189 to-155 in KLF15 promoter, respectively, thus regulate the transcription of KLF15 gene.
低密度脂蛋白受体相关蛋白5基因(low-density lipoprotein receptor related protein 5, LRP5)定位于人类染色体11q13,有23个外显子,编码一个属于低密度脂蛋白受体超家族的含有1615个氨基酸的单个跨膜受体蛋白。LRP5在成人和胚胎组织中广泛表达,其中肝脏表达最高。在骨骼组织中,LRP5主要在骨内膜和小梁骨表面的成骨细胞中表达,而不在破骨细胞中表达。
LRP5在胚胎发育过程中调节多个发育过程,在个体成熟过程中也起着维持生理平衡作用。LRP5基因缺失功能突变导致骨质疏松,而获得功能突变导致骨密度升高,表明LRP5基因在骨形成中发挥着重要的作用,这种作用主要是通过Wnt信号传导通路来完成的。此外,LRP5在血管形成或再生以及正常的脂质代谢和糖代谢中也发挥重要作用。
尽管对LRP5的功能进行了大量研究,但LRP5基因的表达调控机制目前仍不清楚。为此,我们对LRP5基因的表达调控机制进行了分析,取得了以下结果：
1.确定了LRP5基因转录起始点：采用引物延伸方法,我们分析了LRP5基因转录起始点,发现人类LRP5基因的转录起始点位于翻译起始点上游114bp处,距离LRP5基因cDNA序列NM_002335的5′末端40bp处。
2.为寻找LRP5基因转录起始点上游顺式调控元件,我们采用MatInspector和AliBaba 2.1分析软件对LRP5基因翻译起始点上游2495bp片段进行了分析,发现该DNA片段缺乏经典的TATA盒和CAAT盒,但是含有多个可以与Sp1结合的GC盒,以及KLF15,CDE,MAZ,ZBPF等转录因子结合位点。利用荧光素酶报告基因系统,我们分析了该基因组片段在U20S细胞和HEK293细胞中的转录活性,发现该片段具有启动子活性。
3.为了定位启动子核心区域,我们构建了系列截短载体pWT-2015, pWT-1594, pWT-1442, pWT-1309, pWT-1167, pWT-1085, pWT-953, pWT-359, pWT-219, pWT-167, pWT-72, pWT-53和pWT-40,瞬时转染U20S细胞和HEK293细胞并测定荧光素酶活性,结果表明载体在两种细胞中的转录活性趋势一致,提示这些区域内不含有组织特异性调控元件。对比分析不同截短载体表达活性发现人类LRP5基因的基本启动子位于-72至-53之间。
4.软件分析发现在-72至-53之间存在一个KLF15识别结合位点和一个Spl识别结合位点,且两个位点部分重叠。为确定二者在LRP5基因转录调控中的作用,我们构建了两个位点单突变和双突变表达载体,荧光素酶活性分析表明KLF15结合位点和Sp1结合位点是决定LRP5基因基本启动子活性所必需的。
5. EMSA分析发现,包含-72至-53区域的野生型探针能特异性地结合核蛋白,非标记的野生型探针能有效竞争标记探针与核蛋白形成复合物,而非标记的突变型探针则无明显竞争作用,说明该区域的KLF15和Sp1结合位点能特异性结合核蛋白。利用抗Sp1抗体和抗KLF15抗体进行ChIP分析,发现在两个抗体沉淀的染色质复合物中能检测到-72至-53区域DNA片段,进一步证实该区域能特异性与KLF15和Sp1结合。
6.在缺乏KLF15和Sp1蛋白的Drosophila SL2细胞株中共转染pPac-KLF15或者pPac-Sp1表达载体,发现Sp1或KLF15增加LRP5基因启动子活性依赖于LRP5基因-72至-53bp区相应结合位点的存在。
以上研究从Sp1和KLF15结合序列到转录因子以及转录因子与结合位点结合等方面证实LRP5基因-72bp-53bp区域内的Sp1和KLF15结合位点是人LRP5基因启动子功能的所需要的。
第二部分KLF15调节内源性LRR5基因表达
KLF15属于锌指蛋白转录因子家族,既具有转录激活作用,又具有转录抑制作用。本文第一部分利用报告基因分析方法发现,KLF15和Spl共同激活LRP5基因转录。为进一步证实KLF15在生理状态下也可调控LRP5基因转录,本部分以C2C12细胞株为研究对象,该细胞株属于小鼠骨骼肌成肌细胞系,具有多种分化潜能。可以在不同条件诱导下分化为肌管、脂肪细胞和成骨细胞。采用适时定量PCR和Western blotting分析不同诱导分化条件下KLF15表达情况及其对LRP5的转录调控作用,取得了以下结果：
1.用含有2%马血清的DMEM培养基能诱导C2C12细胞分化为肌管,可以观察到细胞形态由典型的梭形和多角形的成纤维样细胞分化为呈平行排列走向,相互融合形成中央核的多核性长管状初生肌管；实时定量PCR检测到肌管的标志基因myogenin表达明显上调。在C2C12诱导分化为肌管过程中,KLF15的mRNA和蛋白质表达水平明显增高,LRP5 mRNA表达水平也明显增加。
2.用5μM的罗格列酮生长培养基能诱导C2C12细胞分化为脂肪细胞,油红0染色可以观察到明显的脂肪细胞产生的脂滴；实时定量PCR检测到脂肪细胞标志基因aP2表达明显上调。在C2C12向脂肪细胞分化过程中,KLF15的mRNA和蛋白质表达水平明显增高,LRP5 mRNA表达水平也明显增加。
3.用成骨培养基能诱导C2C12细胞分化为成骨细胞,茜素红染色可以观察到骨结节形成；实时定量PCR检测到成骨细胞标志基因ALP表达明显上调。在C2C12向成骨细胞分化过程中,KLF15的mRNA和蛋白质表达水平均明显增高,LRP5mRNA表达水平也明显增加。
通过分析C2C12细胞诱导分化为肌管、脂肪细胞和成骨细胞过程中KLF15和LRP5的表达变化,进一步证实LRP5是KLF15转录因子的靶基因,KLF15可以激活LRP5基因转录。
第三部分人类KLF15基因的转录调控机制研究
如前所述,KLF15可以激活基因转录,也可以抑制某些基因转录。前两部分结果均显示KLF15可以在多种细胞分化过程中上调并激活LRP5基因转录。但是到目前为止,对KLF15的转录调控机制尚不明确。为此,本部分对KLF15基因的转录调控机制进行了分析。
1.采用MatInspector和AliBaba 2.1网上软件对KLF15基因启动子区域序列进行分析,发现KLF15启动子缺乏经典的TATA盒,但是富含可以结合Sp1的GC盒子,同时也含有USF1、Smad 4、AP2、CREB、Smad3和NFY等识别结合位点。
2.采用荧光素酶报告基因分析系统,我们构建了序列截短荧光素酶报告基因表达载体pGL3-1804, pGL3-1505, pGL3-863, pGL3-792, pGL3-514, pGL3-217,pGL3-189, pGL3-80, pGL3-45和pGL3-5,瞬时转染HEK293细胞后测定荧光素酶活性。分析这些表达载体荧光素酶表达活性发现人类KLF15基因的转录调控关键元件位于转录起始点上游-189至-80和-80至-45之间的两个区域。
3.软件分析发现-189至-80区域内含有四个GC盒,分别命名为GC1、GC2、GC3和GC4。突变分析发现,GC2和GC3起主要作用,GCl位点作用较小,但在GC2或GC3突变后GC1可能发挥替代作用。
4.在-80至-45之间存在一个E-box保守序列和一个CREB识别结合位点,且两个位点部分重叠。缺失和突变分析发现,E-box是维持人类KLF15基因启动子活性所必需的。利用RNA干扰CREB基因实验排除了该区域CREB识别结合位点的作用。
5. EMSA分析证明-189至-155区域内的GC盒序列可以与核蛋白形成特异性DNA蛋白质复合物,未标记的野生型探针能有效竞争复合物形成,而未标记的突变型探针不影响复合物形成。ChIP分析也证实该区域序列能特异性与Spl蛋白结合。
6. EMSA分析证明-80至-45区域内的E-BOX能与核蛋白结合形成特异性DNA蛋白质复合物,未标记的野生型探针能有效竞争复合物形成,而未标记突变探针不影响复合物形成。ChIP实验进一步证实该区域可以特异性与转录因子USF1结合。
综上所述,本研究采用缺失和突变分析、EMSA、ChIP分析等方法证实USF1和SP1通过分别与KLF15基因启动子近侧-80至-45区域内的E-box和-189至-155区域的GC-box结合调节KLF15基因转录。
Part 1. Regulation of human LRP5 gene transcription
LRP5 (low-density lipoprotein receptor related protein 5), located on human chromosome 11ql3, contains 23 exons encoding a 1615 amino acid single-pass transmembrane receptor that belongs to the low density lipoprotein (LDL) receptor superfamily. LRP5 is expressed in multiple adult and embryonic tissues with strongest expression occurring in the live. In bone, it is expressed by osteoblasts of the endosteal and trabecular bone surfaces but not osteoclasts.
LRP5 regulates diverse developmental processes in embryogenesis and maintains physiological homeostasis in maturity. Loss-of-function mutation in LRP5 can result in osteoporosis, and gain-of-function mutation leads to high bone mass (HBM), indicating that LRP5 plays an important role in bone formation. Such role is through the Wnt signaling pathway. In addition to these roles, the LRP5 is also required for normal cholesterol and glucose metabolism.
Despite lots of effort has been done in study of function of LRP5, the molecular regulation of LRP5 expression remains unclear. Therefore, we studied the transcriptional regulation of LRP5 and got the following results:
1. Determination of the transcriptional start site of LRP5 gene. Using primer extension, we identified the transcriptional start site of LRP5 gene, and found that the transcriptional start site is located at the 114bp upstream of the translational start site,40 nucleotides upstream of the 5'end of the published cDNA sequence (GenBank accession no. NM002335).
2. In order to identify putative transcriptional factor binding sites, we analyzed a 2495bp region upstream of translational start site of LRP5 using the programs Matlnspector (www.genomatix.de/products/MatInspector/) and AliBaba 2.1 (www.gene-regulation.com/pub/programs.html), and failed to find any canonical TATA box or CAAT-like sequence. However, several potential transcription factor binding motifs were identified in the promoter region close to transcription start site, including Sp1, KLF15, CDE, MAZ, and ZBPF. Using luciferase reporter gene, we tested the transcriptional activity of this fragment in U2OS cells and HEK293 cells, and found this region has promoter activity.
3. To determine the minimal region required for basal activity of the promoter, a series of deletion constructs were generated and designated as pWT-2015, pWT-1594, pWT-1442, pWT-1309, pWT-1167, pWT-1085, pWT-953, pWT-359, pWT-219, pWT-72, pWT-53 and pWT-40 based on their variable 5'end. These constructs were tested for their ability to drive the luciferase reporter gene in transiently transfected U2OS and HEK293 cells. Similar trends were observed in these two cell lines, suggesting that cell-specific element may not be present in those sequences. Comparing the expression activity of different deletion constructs, the proximal promoter has been located at-72 and-53.
4. With software analysis, two overlapped transcriptional factor binding sites, one for KLF15 and the other for Sp1, were found in-72 to-53. To determine the contribution of the Spl and/or KLF15 sites to the promoter activity, constructs with either single or double mutant reporters were generated. The luciferase activity assay showed both KLF15 and Spl binding sites between-72 and-53 of human LRP5 promoter contributes to the basal activity of human LRP5 transcription.
5. It is found in EMSA that wild type probe containing the region-72 to-53 can specificly binds to nuclear proteins. Unlabeled wild type probe can effectively abolish the complex of labeled probe and nuclear protein, while unlabeled mutant probe can't, indicating that the KLF15 and Spl sites can specificly bind to nuclear proteins. In ChIP analysis using anti-Sp1 and anti-KLF15 antibodies, DNA fragment from-72 to-53 can be detected from co-immunoprecipitated chromatin complex. This result further confirmed this region can specificly bind to KLF15 and Sp1.
6. By co-transfecting Drosophila SL2 cells lacking KLF15 and Spl proteins with pPac-KLF15 and pPac-Spl, it is found that the increase of LRP5 promoter activity by Spl or KLF15 relies on the existence of corresponding binding sites in-72 to-53.
The foregoing study from different aspects, including the binding sites of Spl and KLF15, transcription factor and their binding, proved the Spl and KLF15 binding sites in-72 to-53 of LRP5 gene are essential for its promoter activity.
Part 2. KLF15 regulates the transcription of endogenous LRP5
Kruppel-like factors (KLFs), a subclass of the zinc-finger family of transcriptional regulators, can function as transcriptional activators and/or repressors depending on promoter context. In the first part, we demonstrated that both KLF15 and Sp1 functions as a positive regulatory element and activates the human LRP5 promoter. C2C12 cell line, a muscle satellite cell line, can differentiate into myotubes, adipocytes and osteoblasts under different condition. Using quantitative PCR and Western blotting, the expression of KLF15 and its regulation of transcription of LRP5 under different differentiating condition were detected, and the results are as following.
1. C2C12 cell matained in DMEM medium with 2% horse serum was induced to the typical morphology of multinucleated myotube. Myotube-specific myogenin gene was dramaticlly upregulated during myogenic differentiation as determined by real-time PCR. During myogenic differentiation, both mRNA and protein of KLF15 were significantly increased. Consequently, LRP5 transcription was significantly upregulated.
2. C2C12 cells matained in the adipogenic medium containg 5μM rosiglitazone became adipose-like morphology and contain lipid droplet which can be stained with Oil red O. The successful induction was confirmed by the significant upregulation of aP2 mRNA, an adipose-sepcific marker, during the adipogenic differentiation. The KLF15 expression was significantly upregulated at both mRNA and protein levels. LRP5 mRNA level was also increased during the adipogenic differentiation.
3. C2C12 matained in osteogenic differentiation medium was induced to differentiate toward osteoblast. On day 24 after treatment, the mineralized nodules were detected by Alizarin red staining. The ALP mRNA, osteoblast-specific gene, was upregulated during the differentiation process. Both mRNA and protein levels of KLF15 gene were significantly induced during differentiation. Consequently, LRP5 mRNA was significantly upregulated.
Taken together, inducing C2C12 cells to differentiate toward myogenis, adipogenis and osteogenis can alter the expression of KLF15 and LRP5. These further confirmed that LRP5 is the target gene of KLF15 and KLF15 can activate the transcription of LRP5 gene.
Part 3. Regulation of human KLF15 gene transcription
KLF15 can activate, as well as repress, gene transcription. The results of last two parts all showed KLF15 can be upregulated during cell differentiation and activate the transcription of LRP5 gene. However, the regulation of transcription of KLF15 is still unknown. Therefore, in this part we studied the regulation mechanism of KLF15 transcription.
1. Using the programs MatInspector (www.genomatix.de/products/MatInspector/) and AliBaba 2.1 (www.gene-regulation.com/pub/programs.html) to analyze the promoter sequence of KLF15 gene, we failed to find any canonical TATA box. However, multiple potential transcription factor binding motifs were identified, including five GC-boxes that can bind to Spl, as well as USF1, CREB, Smad3, Smad4, AP2, and NYF sites.
2. Serial deletion constructs with luciferase reporter gene, pGL3-1804, pGL3-1505, pGL3-863, pGL3-792, pGL3-514, pGL3-217, pGL3-189, pGL3-80, pGL3-45 and pGL3-5, were generated, and luciferase activity were measured after transient transfecting these constructs into HEK293 cells. According to the luciferase activity of these deletion constructs, it is found that the proximal transcription regulator is located in-189 to-80 and-80 to-45.
3. Four GC boxes, designated as GC1, GC2, GC3 and GC4, were found within-189 to-80 by software analysis. Through site-direct mutagenesis, we found GC2 and GC3 play an important role in regulation of KLF15 transcription. The effect of GC1 is not so strong, but might become important after GC2 or GC3 mutated.
4. There are two partially overlapping sites, one E-box consensus sequence and one CREB binding sits within-80 to-45. After deletion and mutation, E-box was found as an essential element that maintains the promoter activity of human KLF15 gene. The possibility of effect of CREB on promoter activity was excluded using RNA interference of CREB.
5. EMSA results showed that GC boxs located in-189 to-155 can form specific DNA-protein complex with nuclear protein. Unlabeled wild type probe can effectively abolish this complex, whereas the unlabeled mutant probe can't. ChIP results also confirmed that Spl protein can specificly bind to this region.
6. Also with EMSA was E-Box found to be able to form specific DNA-protein complex. Unlabeled wild type probe can effectively abolish this complex, whereas the unlabeled mutant probe can't. ChIP results also confirmed that transcription factor USF1 can specificly bind to this region.
In summary, this study adopting different approaches, such as deletion and mutation analysis, EMSA, ChIP, to prove that USF1 and Spl can bind to E-box in-80 to-45 and GC-box in-189 to-155 in KLF15 promoter, respectively, thus regulate the transcription of KLF15 gene.
引文
1 Krieger M, Herz J:Structures and functions of multiligand lipoprotein receptors:macrophage scavenger receptors and LDL receptor-related protein (LRP). Annu Rev Biochem 1994,63:601-637.
2 Herz J, Willnow TE:Functions of the LDL receptor gene family. Ann N Y Acad Sci 1994,737:14-19.
3 Brown MS, Herz J, Goldstein JL:LDL-receptor structure. Calcium cages, acid baths and recycling receptors. Nature 1997,388:629-630.
4 Dong Y, Lathrop W, Weaver D, Qiu Q, Cini J, Bertolini D, Chen D:Molecular cloning and characterization of LR3, a novel LDL receptor family protein with mitogenic activity. Biochem Biophys Res Commun 1998,251:784-790.
5 Chen D, Lathrop W, Dong Y:Molecular cloning of mouse Lrp7(Lr3) cDNA and chromosomal mapping of orthologous genes in mouse and human. Genomics 1999,55:314-321.
6 Hey PJ, Twells RC, Phillips MS, Yusuke N, Brown SD, Kawaguchi Y, Cox R, Guochun X, Dugan V, Hammond H, Metzker ML, Todd JA, Hess JF:Cloning of a novel member of the low-density lipoprotein receptor family. Gene 1998,216:103-111.
7 Kato M, Patel MS, Levasseur R, Lobov I, Chang BH, Glass DA,2nd, Hartmann C, Li L, Hwang TH, Brayton CF, Lang RA, Karsenty G, Chan L: Cbfal-independent decrease in osteoblast proliferation, osteopenia, and persistent embryonic eye vascularization in mice deficient in Lrp5, a Wnt coreceptor. J Cell Biol 2002,157:303-314.
8 Figueroa DJ, Hess JF, Ky B, Brown SD, Sandig V, Hermanowski-Vosatka A, Twells RC, Todd JA, Austin CP:Expression of the type I diabetes-associated gene LRP5 in macrophages, vitamin A system cells, and the Islets of Langerhans suggests multiple potential roles in diabetes. J Histochem Cytochem 2000,48:1357-1368.
9 Boyden LM, Mao J, Belsky J, Mitzner L, Farhi A, Mitnick MA, Wu D, Insogna K, Lifton RP:High bone density due to a mutation in LDL-receptor-related protein 5. NEngl JMed 2002,346:1513-1521.
10 Little RD, Carulli JP, Del Mastro RG, Dupuis J, Osborne M, Folz C, Manning SP, Swain PM, Zhao SC, Eustace B, Lappe MM, Spitzer L, Zweier S, Braunschweiger K, Benchekroun Y, Hu X, Adair R, Chee L, FitzGerald MG, Tulig C, Caruso A, Tzellas N, Bawa A, Franklin B, McGuire S, Nogues X, Gong G, Allen KM, Anisowicz A, Morales AJ, Lomedico PT, Recker SM, Van Eerdewegh P, Recker RR, Johnson ML:A mutation in the LDL receptor-related protein 5 gene results in the autosomal dominant high-bone-mass trait. Am JHum Genet 2002,70:11-19.
11 Van Wesenbeeck L, Cleiren E, Gram J, Beals RK, Benichou O, Scopelliti D, Key L, Renton T, Bartels C, Gong Y, Warman ML, De Vernejoul MC, Bollerslev J, Van Hul W:Six novel missense mutations in the LDL receptor-related protein 5 (LRP5) gene in different conditions with an increased bone density. Am J Hum Genet 2003,72:763-771.
12 Gong Y, Slee RB, Fukai N, Rawadi G, Roman-Roman S, Reginato AM, Wang H, Cundy T, Glorieux FH, Lev D, Zacharin M, Oexle K, Marcelino J, Suwairi W, Heeger S, Sabatakos G, Apte S, Adkins WN, Allgrove J, Arslan-Kirchner M, Batch JA, Beighton P, Black GC, Boles RG, Boon LM, Borrone C, Brunner HG, Carle GF, Dallapiccola B, De Paepe A, Floege B, Halfhide ML, Hall B, Hennekam RC, Hirose T, Jans A, Juppner H, Kim CA, Keppler-Noreuil K, Kohlschuetter A, LaCombe D, Lambert M, Lemyre E, Letteboer T, Peltonen L, Ramesar RS, Romanengo M, Somer H, Steichen-Gersdorf E, Steinmann B, Sullivan B, Superti-Furga A, Swoboda W, van den Boogaard MJ, Van Hul W, Vikkula M, Votruba M, Zabel B, Garcia T, Baron R, Olsen BR, Warman ML: LDL receptor-related protein 5 (LRP5) affects bone accrual and eye development. Cell 2001,107:513-523.
13 Jiao X, Ventruto V, Trese MT, Shastry BS, Hejtmancik JF:Autosomal recessive familial exudative vitreoretinopathy is associated with mutations in LRP5. Am J Hum Genet 2004,75:878-884.
14 Qin M, Hayashi H, Oshima K, Tahira T, Hayashi K, Kondo H:Complexity of the genotype-phenotype correlation in familial exudative vitreoretinopathy with mutations in the LRP5 and/or FZD4 genes. Hum Mutat 2005, 26:104-112.
15 Toomes C, Bottomley HM, Jackson RM, Towns KV, Scott S, Mackey DA, Craig JE, Jiang L, Yang Z, Trembath R, Woodruff Q Gregory-Evans CY, Gregory-Evans K, Parker MJ, Black GC, Downey LM, Zhang K, Inglehearn CF: Mutations in LRP5 or FZD4 underlie the common familial exudative vitreoretinopathy locus on chromosome 11 q. Am J Hum Genet 2004, 74:721-730.
16 Haines JL, Schnetz-Boutaud N, Schmidt S, Scott WK, Agarwal A, Postel EA, Olson L, Kenealy SJ, Hauser M, Gilbert JR, Pericak-Vance MA:Functional candidate genes in age-related macular degeneration:significant association with VEGF, VLDLR, and LRP6. Invest Ophthalmol Vis Sci 2006, 47:329-335.
17 Kadonaga JT, Carner KR, Masiarz FR, Tjian R:Isolation of cDNA encoding transcription factor Spl and functional analysis of the DNA binding domain. Cell 1987,51:1079-1090.
18 Briggs MR, Kadonaga JT, Bell SP, Tjian R:Purification and biochemical characterization of the promoter-specific transcription factor, Spl. Science 1986,234:47-52.
19 Letovsky J, Dynan WS:Measurement of the binding of transcription factor Spl to a single GC box recognition sequence. Nucleic Acids Res 1989, 17:2639-2653.
20 Dunah AW, Jeong H, Griffin A, Kim YM, Standaert DG, Hersch SM, Mouradian MM, Young AB, Tanese N, Krainc D:Spl and TAFII130 transcriptional activity disrupted in early Huntington's disease. Science 2002, 296:2238-2243.
21 Torigoe T, Izumi H, Yoshida Y, Ishiguchi H, Okamoto T, Itoh H, Kohno K:Low pH enhances Spl DNA binding activity and interaction with TBP. Nucleic Acids Res 2003,31:4523-4530.
22 Marin M, Karis A, Visser P, Grosveld F, Philipsen S:Transcription factor Spl is essential for early embryonic development but dispensable for cell growth and differentiation. Cell 1997,89:619-628.
23 Black AR, Black JD, Azizkhan-Clifford J:Spl and kruppel-like factor family of transcription factors in cell growth regulation and cancer. J Cell Physiol 2001,188:143-160.
24 Bieker JJ:Kruppel-like factors:three fingers in many pies. JBiol Chem 2001, 276:34355-34358.
25 Kaczynski J, Cook T, Urrutia R:Spl-and Kruppel-like transcription factors. Genome Biol 2003,4:206.
26 Cook T, Gebelein B, Belal M, Mesa K, Urrutia R:Three conserved transcriptional repressor domains are a defining feature of the TIEG subfamily of Spl-like zinc finger proteins. J Biol Chem 1999, 274:29500-29504.
27 Gray S, Feinberg MW, Hull S, Kuo CT, Watanabe M, Sen-Banerjee S, DePina A, Haspel R, Jain MK:The Kruppel-like factor KLF15 regulates the insulin-sensitive glucose transporter GLUT4. J Biol Chem 2002, 277:34322-34328.
28 Otteson DC, Liu Y, Lai H, Wang C, Gray S, Jain MK, Zack DJ:Kruppel-like factor 15, a zinc-finger transcriptional regulator, represses the rhodopsin and interphotoreceptor retinoid-binding protein promoters. Invest Ophthalmol Vis Sci 2004,45:2522-2530.
29 Uchida S, Tanaka Y, Ito H, Saitoh-Ohara F, Inazawa J, Yokoyama KK, Sasaki S, Marumo F:Transcriptional regulation of the CLC-K1 promoter by myc-associated zinc finger protein and kidney-enriched Kruppel-like factor, a novel zinc finger repressor. Mol Cell Biol 2000,20:7319-7331.
30 Yamamoto J, Ikeda Y, Iguchi H, Fujino T, Tanaka T, Asaba H, Iwasaki S, Ioka RX, Kaneko IW, Magoori K, Takahashi S, Mori T, Sakaue H, Kodama T, Yanagisawa M, Yamamoto TT, Ito S, Sakai J:A Kruppel-like factor KLF15 contributes fasting-induced transcriptional activation of mitochondrial acetyl-CoA synthetase gene AceCS2. JBiol Chem 2004,279:16954-16962.
31 Katagiri T, Yamaguchi A, Komaki M, Abe E, Takahashi N, Ikeda T, Rosen V, Wozney JM, Fujisawa-Sehara A, Suda T:Bone morphogenetic protein-2 converts the differentiation pathway of C2C12 myoblasts into the osteoblast lineage. J Cell Biol 1994,127:1755-1766.
32 Johnson ML:The high bone mass family-the role of Wnt/Lrp5 signaling in the regulation of bone mass. J Musculoskelet Neuronal Interact 2004, 4:135-138.
33 Grimaldi PA, Teboul L, Inadera H, Gaillard D, Amri EZ:Trans-differentiation of myoblasts to adipoblasts:triggering effects of fatty acids and thiazolidinediones. Prostaglandins Leukot Essent Fatty Acids 1997,57:71-75.
34 Tontonoz P, Hu E, Spiegelman BM:Stimulation of adipogenesis in fibroblasts by PPAR gamma 2, a lipid-activated transcription factor. Cell 1994, 79:1147-1156.
35 De Coppi P, Milan G, Scarda A, Boldrin L, Centobene C, Piccoli M, Pozzobon M, Pilon C, Pagano C, Gamba P, Vettor R:Rosiglitazone modifies the adipogenic potential of human muscle satellite cells. Diabetologia 2006, 49:1962-1973.
36 Uchida S, Rai T, Yatsushige H, Matsumura Y, Kawasaki M, Sasaki S, Marumo F: Isolation and characterization of kidney-specific ClC-K1 chloride channel gene promoter. Am JPhysiol 1998,274:F602-610.
37 Rai T, Uchida S, Sasaki S, Marumo F:Isolation and characterization of kidney-specific CLC-K2 chloride channel gene promoter. Biochem Biophys Res Commun 1999,261:432-438.
38 Nakamura T, Alder H, Gu Y, Prasad R, Canaani O, Kamada N, Gale RP, Lange B, Crist WM, Nowell PC, et al.:Genes on chromosomes 4,9, and 19 involved in 11q23 abnormalities in acute leukemia share sequence homology and/or common motifs. Proc Natl Acad Sci USA 1993,90:4631-4635.
39 Licht JD, Grossel MJ, Figge J, Hansen UM:Drosophila Kruppel protein is a transcriptional repressor. Nature 1990,346:76-79.
40 Madden SL, Cook DM, Rauscher FJ,3rd:A structure-function analysis of transcriptional repression mediated by the WT1, Wilms'tumor suppressor protein. Oncogene 1993,8:1713-1720.
41 Witzgall R, O'Leary E, Leaf A, Onaldi D, Bonventre JV:The Kruppel-associated box-A (KRAB-A) domain of zinc finger proteins mediates transcriptional repression. Proc Natl Acad Sci U S A 1994, 91:4514-4518.
42 Saha S, Brickman JM, Lehming N, Ptashne M:New eukaryotic transcriptional repressors. Nature 1993,363:648-652.
43 Woods A, James CG, Wang G, Dupuis H, Beier F:Control of Chondrocyte Gene Expression by Actin Dynamics:A Novel Role of Cholesterol/Roralpha Signaling in Endochondral Bone Growth. J Cell Mol Med 2009.
44 Otteson DC, Lai H, Liu Y, Zack DJ:Zinc-finger domains of the transcriptional repressor KLF15 bind multiple sites in rhodopsin and IRBP promoters including the CRS-1 and G-rich repressor elements. BMC Mol Biol 2005,6:15.
45 Suske G:The Sp-family of transcription factors. Gene 1999,238:291-300.
46 Viollet B, Lefrancois-Martinez AM, Henrion A, Kahn A, Raymondjean M, Martinez A:Immunochemical characterization and transacting properties of upstream stimulatory factor isoforms. J Biol Chem 1996,271:1405-1415.
47 Gregor PD, Sawadogo M, Roeder RG:The adenovirus major late transcription factor USF is a member of the helix-loop-helix group of regulatory proteins and binds to DNA as a dimer. Genes Dev 1990, 4:1730-1740.
48 Sawadogo M:Multiple forms of the human gene-specific transcription factor USF. Ⅱ. DNA binding properties and transcriptional activity of the purified HeLa USF. JBiol Chem 1988,263:11994-12001.
49 Sawadogo M, Van Dyke MW, Gregor PD, Roeder RG:Multiple forms of the human gene-specific transcription factor USF. Ⅰ. Complete purification and identification of USF from HeLa cell nuclei. J Biol Chem 1988, 263:11985-11993.
50 Shieh BH, Sparkes RS, Gaynor RB, Lusis AJ:Localization of the gene-encoding upstream stimulatory factor (USF) to human chromosome 1q22-q23. Genomics 1993,16:266-268.
51 Groenen PM, Garcia E, Debeer P, Devriendt K, Fryns JP, Van de Ven WJ: Structure, sequence, and chromosome 19 localization of human USF2 and its rearrangement in a patient with multicystic renal dysplasia. Genomics 1996,38:141-148.
52 Sirito M, Lin Q, Maity T, Sawadogo M:Ubiquitous expression of the 43-and 44-kDa forms of transcription factor USF in mammalian cells. Nucleic Acids Res 1994,22:427-433.
53 Sirito M, Walker S, Lin Q, Kozlowski MT, Klein WH, Sawadogo M:Members of the USF family of helix-loop-helix proteins bind DNA as homo-as well as heterodimers. Gene Expr 1992,2:231-240.
54 Virolle T, Coraux C, Ferrigno O, Cailleteau L, Ortonne JP, Pognonec P, Aberdam D:Binding of USF to a non-canonical E-box following stress results in a cell-specific derepression of the lama3 gene. Nucleic Acids Res 2002,30:1789-1798.
55 Ge Y, Jensen TL, Matherly LH, Taub JW:Physical and functional interactions between USF and Spl proteins regulate human deoxycytidine kinase promoter activity. J Biol Chem 2003,278:49901-49910.
56 Coulson JM, Edgson JL, Marshall-Jones ZV, Mulgrew R, Quinn JP, Woll PJ: Upstream stimulatory factor activates the vasopressin promoter via multiple motifs, including a non-canonical E-box. Biochem J 2003, 369:549-561.
57 Pawar SA, Szentirmay MN, Hermeking H, Sawadogo M:Evidence for a cancer-specific switch at the CDK4 promoter with loss of control by both USF and c-Myc. Oncogene 2004,23:6125-6135.
58 Galibert MD, Carreira S, Goding CR:The Usf-1 transcription factor is a novel target for the stress-responsive p38 kinase and mediates UV-induced Tyrosinase expression. Embo J2001,20:5022-5031.
59 Henrion AA, Martinez A, Mattei MG, Kahn A, Raymondjean M:Structure, sequence, and chromosomal location of the gene for USF2 transcription factors in mouse. Genomics 1995,25:36-43.
60 Li N, Seetharam B:A 69-base pair fragment derived from human transcobalamin Ⅱ promoter is sufficient for high bidirectional activity in the absence of a TATA box and an initiator element in transfected cells. Role of an E box in transcriptional activity. J Biol Chem 1998, 273:28170-28177.
61 Ge Y, Konrad MA, Matherly LH, Taub JW:Transcriptional regulation of the human cystathionine beta-synthase-lb basal promoter:synergistic transactivation by transcription factors NF-Y and Spl/Sp3. Biochem J 2001, 357:97-105.
62 Brown MS, Goldstein JL:Receptor-mediated endocytosis:insights from the lipoprotein receptor system. Proc Natl Acad Sci USA 1979,76:3330-3337.
63 Sakai J, Hoshino A, Takahashi S, Miura Y, Ishii H, Suzuki H, Kawarabayasi Y, Yamamoto T:Structure, chromosome location, and expression of the human very low density lipoprotein receptor gene. J Biol Chem 1994, 269:2173-2182.
64 Herz J, Hamann U, Rogne S, Myklebost O, Gausepohl H, Stanley KK:Surface location and high affinity for calcium of a 500-kd liver membrane protein closely related to the LDL-receptor suggest a physiological role as lipoprotein receptor. Embo J1988,7:4119-4127.
65 Liu CX, Musco S, Lisitsina NM, Forgacs E, Minna JD, Lisitsyn NA:LRP-DIT, a putative endocytic receptor gene, is frequently inactivated in non-small cell lung cancer cell lines. Cancer Res 2000,60:1961-1967.
66 Ishii H, Kim DH, Fujita T, Endo Y, Saeki S, Yamamoto TT:cDNA cloning of a new low-density lipoprotein receptor-related protein and mapping of its gene (LRP3) to chromosome bands 19q12-q13.2. Genomics 1998, 51:132-135.
67 Tomita Y, Kim DH, Magoori K, Fujino T, Yamamoto TT:A novel low-density lipoprotein receptor-related protein with type II membrane protein-like structure is abundant in heart. J Biochem 1998,124:784-789.
68 Brown SD, Twells RC, Hey PJ, Cox RD, Levy ER, Soderman AR, Metzker ML, Caskey CT, Todd JA, Hess JF:Isolation and characterization of LRP6, a novel member of the low density lipoprotein receptor gene family. Biochem Biophys Res Commun 1998,248:879-888.
69 Hjalm G, Murray E, Crumley G, Harazim W, Lundgren S, Onyango I, Ek B, Larsson M, Juhlin C, Hellman P, Davis H, Akerstrom G, Rask L, Morse B: Cloning and sequencing of human gp330, a Ca(2+)-binding receptor with potential intracellular signaling properties. Eur J Biochem 1996, 239:132-137.
70 Kim DH, Iijima H, Goto K, Sakai J, Ishii H, Kim HJ, Suzuki H, Kondo H, Saeki S, Yamamoto T:Human apolipoprotein E receptor 2. A novel lipoprotein receptor of the low density lipoprotein receptor family predominantly expressed in brain. J Biol Chem 1996,271:8373-8380.
71 Jacobsen L, Madsen P, Moestrup SK, Lund AH, Tommerup N, Nykjaer A, Sottrup-Jensen L, Gliemann J, Petersen CM:Molecular characterization of a novel human hybrid-type receptor that binds the alpha2-macroglobulin receptor-associated protein. JBiol Chem 1996,271:31379-31383.
72 Doubleday AF, Kaestle FA, Cox LA, Birnbaum S, Mahaney MC, Havill LM: LRP5 sequence and polymorphisms in the baboon. J Med Primatol 2009, 38:97-106.
73 Gliemann J:Receptors of the low density lipoprotein (LDL) receptor family in man. Multiple functions of the large family members via interaction with complex ligands. Biol Chem 1998,379:951-964.
74 Somer H, Palotie A, Somer M, Hoikka V, Peltonen L: Osteoporosis-pseudoglioma syndrome:clinical, morphological, and biochemical studies. JMed Genet 1988,25:543-549.
75 De Paepe A, Leroy JG, Nuytinck L, Meire F, Capoen J: Osteoporosis-pseudoglioma syndrome. Am JMed Genet 1993,45:30-37.
76 Johnson ML, Gong G, Kimberling W, Recker SM, Kimmel DB, Recker RB: Linkage of a gene causing high bone mass to human chromosome 11 (11q12-13). Am J Hum Genet 1997,60:1326-1332.
77 Mizuguchi T, Furuta I, Watanabe Y, Tsukamoto K, Tomita H, Tsujihata M, Ohta T, Kishino T, Matsumoto N, Minakami H, Niikawa N, Yoshiura K:LRP5, low-density-lipoprotein-receptor-related protein 5, is a determinant for bone mineral density. JHum Genet 2004,49:80-86.
78 Ezura Y, Nakajima T, Urano T, Sudo Y, Kajita M, Yoshida H, Suzuki T, Hosoi T, Inoue S, Shiraki M, Emi M:Association of a single-nucleotide variation (A1330V) in the low-density lipoprotein receptor-related protein 5 gene (LRP5) with bone mineral density in adult Japanese women. Bone 2007, 40:997-1005.
79 Balemans W, Van Hul W:The genetics of low-density lipoprotein receptor-related protein 5 in bone:a story of extremes. Endocrinology 2007, 148:2622-2629.
80 Richards JB, Rivadeneira F, Inouye M, Pastinen TM, Soranzo N, Wilson SG, Andrew T, Falchi M, Gwilliam R, Ahmadi KR, Valdes AM, Arp P, Whittaker P, Verlaan DJ, Jhamai M, Kumanduri V, Moorhouse M, van Meurs JB, Hofrnan A, Pols HA, Hart D, Zhai G, Kato BS, Mullin BH, Zhang F, Deloukas P, Uitterlinden AG, Spector TD:Bone mineral density, osteoporosis, and osteoporotic fractures:a genome-wide association study. Lancet 2008, 371:1505-1512.
81 Urano T, Shiraki M, Ezura Y, Fujita M, Sekine E, Hoshino S, Hosoi T, Orimo H, Emi M, Ouchi Y, Inoue S:Association of a single-nucleotide polymorphism in low-density lipoprotein receptor-related protein 5 gene with bone mineral density. J Bone Miner Metab 2004,22:341-345.
82 Ferrari SL, Deutsch S, Choudhury U, Chevalley T, Bonjour JP, Dermitzakis ET, Rizzoli R, Antonarakis SE:Polymorphisms in the low-density lipoprotein receptor-related protein 5 (LRP5) gene are associated with variation in vertebral bone mass, vertebral bone size, and stature in whites. Am J Hum Genet 2004,74:866-875.
83 Koh JM, Jung MH, Hong JS, Park HJ, Chang JS, Shin HD, Kim SY, Kim GS: Association between bone mineral density and LDL receptor-related protein 5 gene polymorphisms in young Korean men. J Korean Med Sci 2004,19:407-412.
84 Lau HH, Ng MY, Ho AY, Luk KD, Kung AW:Genetic and environmental determinants of bone mineral density in Chinese women. Bone 2005, 36:700-709.
85 Zhang ZL, Qin YJ, He JW, Huang QR, Li M, Hu YQ, Liu YJ:Association of polymorphisms in low-density lipoprotein receptor-related protein 5 gene with bone mineral density in postmenopausal Chinese women. Acta Pharmacol Sin 2005,26:1111-1116.
86 Lau HH, Ng MY, Cheung WM, Paterson AD, Sham PC, Luk KD, Chan V, Kung AW:Assessment of linkage and association of 13 genetic loci with bone mineral density. JBone Miner Metab 2006,24:226-234.
87 Urano T, Shiraki M, Narusawa K, Usui T, Sasaki N, Hosoi T, Ouchi Y, Nakamura T, Inoue S:Q89R polymorphism in the LDL receptor-related protein 5 gene is associated with spinal osteoarthritis in postmenopausal Japanese women. Spine (Phila Pa 1976) 2007,32:25-29.
88 Urano T:[Regulation of bone metabolism by pathogenic mutations and polymorphism in the LRP5-Wnt signaling genes]. Nippon Rinsho 2007,65 Suppl 9:95-100.
89 Urano T, Shiraki M, Usui T, Sasaki N, Ouchi Y, Inoue S:A1330V variant of the low-density lipoprotein receptor-related protein 5 (LRP5) gene decreases Wnt signaling and affects the total body bone mineral density in Japanese women. Endocr J 2009,56:625-631.
90 Koay MA, Tobias JH, Leary SD, Steer CD, Vilarino-Guell C, Brown MA:The effect of LRP5 polymorphisms on bone mineral density is apparent in childhood. Calcif Tissue Int 2007,81:1-9.
91 Utriainen P, Jaaskelainen J, Saarinen A, Vanninen E, Makitie O, Voutilainen R: Body Composition and Bone Mineral Density in Children with Premature Adrenarche and the Association of LRP5 Gene Polymorphisms with Bone Mineral Density. J Clin Endocrinol Metab 2009.
92 Li Y, Bu G:LRP5, a multifunctional cell surface receptor. Curr Opin Lipidol 2004,15:361-363.
93 Tamai K, Semenov M, Kato Y, Spokony R, Liu C, Katsuyama Y, Hess F, Saint-Jeannet JP, He X:LDL-receptor-related proteins in Wnt signal transduction. Nature 2000,407:530-535.
94 He X, Semenov M, Tamai K, Zeng X:LDL receptor-related proteins 5 and 6 in Wnt/beta-catenin signaling:arrows point the way. Development 2004, 131:1663-1677.
95 Moon RT, Kohn AD, De Ferrari GV, Kaykas A:WNT and beta-catenin signalling:diseases and therapies. Nat Rev Genet 2004,5:691-701.
96 Glass DA,2nd, Bialek P, Ahn JD, Starbuck M, Patel MS, Clevers H, Taketo MM, Long F, McMahon AP, Lang RA, Karsenty G:Canonical Wnt signaling in differentiated osteoblasts controls osteoclast differentiation. Dev Cell 2005,8:751-764.
97 Boonstra FN, van Nouhuys CE, Schuil J, de Wijs IJ, van der Donk KP, Nikopoulos K, Mukhopadhyay A, Scheffer H, Tilanus MA, Cremers FP, Hoefsloot LH:Clinical and molecular evaluation of probands and family members with familial exudative vitreoretinopathy. Invest Ophthalmol Vis Sci 2009,50:4379-4385.
98 Ito M, Yoshioka M:Regression of the hyaloid vessels and pupillary membrane of the mouse. Anat Embryol (Berl) 1999,200:403-411.
99 Xu Q, Wang Y, Dabdoub A, Smallwood PM, Williams J, Woods C, Kelley MW, Jiang L, Tasman W, Zhang K, Nathans J:Vascular development in the retina and inner ear:control by Norrin and Frizzled-4, a high-affinity ligand-receptor pair. Cell 2004,116:883-895.
100 Pinson KI, Brennan J, Monkley S, Avery BJ, Skarnes WC:An LDL-receptor-related protein mediates Wnt signalling in mice. Nature 2000, 407:535-538.
101 Xia CH, Liu H, Cheung D, Wang M, Cheng C, Du X, Chang B, Beutler B, Gong X:A model for familial exudative vitreoretinopathy caused by LPR5 mutations. Hum Mol Genet 2008,17:1605-1612.
102 Lang RA, Bishop JM:Macrophages are required for cell death and tissue remodeling in the developing mouse eye. Cell 1993,74:453-462.
103 Lang RA:Apoptosis in mammalian eye development:lens morphogenesis, vascular regression and immune privilege. Cell Death Differ 1997,4:12-20.
104 Fujino T, Asaba H, Kang MJ, Ikeda Y, Sone H, Takada S, Kim DH, Ioka RX, Ono M, Tomoyori H, Okubo M, Murase T, Kamataki A, Yamamoto J, Magoori K, Takahashi S, Miyamoto Y, Oishi H, Nose M, Okazaki M, Usui S, Imaizumi K, Yanagisawa M, Sakai J, Yamamoto TT:Low-density lipoprotein receptor-related protein 5 (LRP5) is essential for normal cholesterol metabolism and glucose-induced insulin secretion. Proc Natl Acad Sci U S A 2003,100:229-234.
105 Suwazono Y, Kobayashi E, Dochi M, Miura K, Morikawa Y, Ishizaki M, Kido T, Nakagawa H, Nogawa K:Combination of the C1429T polymorphism in the G-protein beta-3 subunit gene and the A1330V polymorphism in the low-density lipoprotein receptor-related protein 5 gene is a risk factor for hypercholesterolaemia. Clin Exp Med 2007,7:108-114.
106 Zenibayashi M, Miyake K, Horikawa Y, Hirota Y, Teranishi T, Kouyama K, Sakaguchi K, Takeda J, Kasuga M:Lack of association of LRP5 and LRP6 polymorphisms with type 2 diabetes mellitus in the Japanese population. Endocr J2008,55:699-707.
107 Bieker JJ:Isolation, genomic structure, and expression of human erythroid Kruppel-like factor (EKLF). DNA Cell Biol 1996,15:347-352.
108 Anderson KP, Kern CB, Crable SC, Lingrel JB:Isolation of a gene encoding a functional zinc finger protein homologous to erythroid Kruppel-like factor: identification of a new multigene family. Mol Cell Biol 1995,15:5957-5965.
109 Suske G, Bruford E, Philipsen S:Mammalian SP/KLF transcription factors: bring in the family. Genomics 2005,85:551-556.
110 Shields JM, Christy RJ, Yang VW:Identification and characterization of a gene encoding a gut-enriched Kruppel-like factor expressed during growth arrest. J Biol Chem 1996,271:20009-20017.
111 Koritschoner NP, Bocco JL, Panzetta-Dutari Gm, Dumur CI, Flury A, Patrito LC:A novel human zinc finger protein that interacts with the core promoter element of a TATA box-less gene. J Biol Chem 1997, 272:9573-9580.
112 Matsumoto N, Laub F, Aldabe R, Zhang W, Ramirez F, Yoshida T, Terada M: Cloning the cDNA for a new human zinc finger protein defines a group of closely related Kruppel-like transcription factors. J Biol Chem 1998, 273:28229-28237.
113 van Vliet J, Turner J, Crossley M:Human Kruppel-like factor 8:a CACCC-box binding protein that associates with CtBP and represses transcription. Nucleic Acids Res 2000,28:1955-1962.
114 Ohe N, Yamasaki Y, Sogawa K, Inazawa J, Ariyama T, Oshimura M, Fujii-Kuriyama Y:Chromosomal localization and cDNA sequence of human BTEB, a GC box binding protein. Somat Cell Mol Genet 1993,19:499-503.
115 Tachibana I, Imoto M, Adjei PN, Gores GJ, Subramaniam M, Spelsberg TC, Urrutia R:Overexpression of the TGFbeta-regulated zinc finger encoding gene, TIEG, induces apoptosis in pancreatic epithelial cells. J Clin Invest 1997,99:2365-2374.
116 Asano H, Li XS, Stamatoyannopoulos G:FKLF, a novel Kruppel-like factor that activates human embryonic and fetal beta-like globin genes. Mol Cell Biol 1999,19:3571-3579.
117 Imhof A, Schuierer M, Werner O, Moser M, Roth C, Bauer R, Buettner R: Transcriptional regulation of the AP-2alpha promoter by BTEB-1 and AP-2rep, a novel wt-1/egr-related zinc finger repressor. Mol Cell Biol 1999, 19:194-204.
118 Scohy S, Gabant P, Van Reeth T, Hertveldt V, Dreze PL, Van Vooren P, Riviere M, Szpirer J, Szpirer C:Identification of KLF13 and KLF14 (SP6), novel members of the SP/XKLF transcription factor family. Genomics 2000, 70:93-101.
119 van Vliet J, Crofts LA, Quinlan KG, Czolij R, Perkins AC, Crossley M:Human KLF17 is a new member of the Sp/KLF family of transcription factors. Genomics 2006,87:474-482.
120 Nuez B, Michalovich D, Bygrave A, Ploemacher R, Grosveld F:Defective haematopoiesis in fetal liver resulting from inactivation of the EKLF gene. Nature 1995,375:316-318.
121 Kuo CT, Veselits ML, Leiden JM:LKLF:A transcriptional regulator of single-positive T cell quiescence and survival. Science 1997,277:1986-1990.
122 Kuo CT, Veselits ML, Barton KP, Lu MM, Clendenin C, Leiden JM:The LKLF transcription factor is required for normal tunica media formation and blood vessel stabilization during murine embryogenesis. Genes Dev 1997,11:2996-3006.
123 Cline GW, Petersen KF, Krssak M, Shen J, Hundal RS, Trajanoski Z, Inzucchi S, Dresner A, Rothman DL, Shulman GI:Impaired glucose transport as a cause of decreased insulin-stimulated muscle glycogen synthesis in type 2 diabetes.
NEngl JMed 1999,341:240-246.
124 Zisman A, Peroni OD, Abel ED, Michael MD, Mauvais-Jarvis F, Lowell BB, Wojtaszewski JF, Hirshman MF, Virkamaki A, Goodyear LJ, Kahn CR, Kahn BB:Targeted disruption of the glucose transporter 4 selectively in muscle causes insulin resistance and glucose intolerance. Nat Med 2000,6:924-928.
125 Abel ED, Peroni O, Kim JK, Kim YB, Boss O, Hadro E, Minnemann T, Shulman GI, Kahn BB:Adipose-selective targeting of the GLUT4 gene impairs insulin action in muscle and liver. Nature 2001,409:729-733.
126 Hauswirth WW, Langerijt AV, Timmers AM, Adamus G, Ulshafer RJ:Early expression and localization of rhodopsin and interphotoreceptor retinoid-binding protein (IRBP) in the developing fetal bovine retina. Exp Eye Res 1992,54:661-670.
127 Araki M, Taketani S:A PCR analysis of rhodopsin gene transcription in rat pineal photoreceptor differentiation. Brain Res Dev Brain Res 1992, 69:149-152.
128 Blackshaw S, Snyder SH:Developmental expression pattern of phototransduction components in mammalian pineal implies a light-sensing function. JNeurosci 1997,17:8074-8082.
129 Sohocki MM, Daiger SP, Bowne SJ, Rodriquez JA, Northrup H, Heckenlively JR, Birch DG, Mintz-Hittner H, Ruiz RS, Lewis RA, Saperstein DA, Sullivan LS:Prevalence of mutations causing retinitis pigmentosa and other inherited retinopathies. Hum Mutat 2001,17:42-51.
130 Lane MD, Tang QQ, Jiang MS:Role of the CCAAT enhancer binding proteins (C/EBPs) in adipocyte differentiation. Biochem Biophys Res Commun 1999,266:677-683.
131 Zhang JW, Tang QQ, Vinson C, Lane MD:Dominant-negative C/EBP disrupts mitotic clonal expansion and differentiation of 3T3-L1 preadipocytes. Proc Natl Acad Sci USA 2004,101:43-47.
132 Mori T, Sakaue H, Iguchi H, Gomi H, Okada Y, Takashima Y, Nakamura K, Nakamura T, Yamauchi T, Kubota N, Kadowaki T, Matsuki Y, Ogawa W, Hiramatsu R, Kasuga M:Role of Kruppel-like factor 15 (KLF15) in transcriptional regulation of adipogenesis. J Biol Chem 2005, 280:12867-12875:
133 Yeh WC, Cao Z, Classon M, McKnight SL:Cascade regulation of terminal adipocyte differentiation by three members of the C/EBP family of leucine zipper proteins. Genes Dev 1995,9:168-181.
134 Wu Z, Bucher NL, Farmer SR:Induction of peroxisome proliferator-activated receptor gamma during the conversion of 3T3 fibroblasts into adipocytes is mediated by C/EBPbeta, C/EBPdelta, and glucocorticoids. Mol Cell Biol 1996,16:4128-4136.
135 Griendling KK, Sorescu D, Ushio-Fukai M:NAD(P)H oxidase:role in cardiovascular biology and disease. Circ Res 2000,86:494-501.
136 Barry-Lane PA, Patterson C, van der Merwe M, Hu Z, Holland SM, Yeh ET, Runge MS:p47phox is required for atherosclerotic lesion progression in ApoE(-/-) mice. JClin Invest 2001,108:1513-1522.
137 Patterson C, Ruef J, Madamanchi NR, Barry-Lane P, Hu Z, Horaist C, Ballinger CA, Brasier AR, Bode C, Runge MS:Stimulation of a vascular smooth muscle cell NAD(P)H oxidase by thrombin. Evidence that p47(phox) may participate in forming this oxidase in vitro and in vivo. J Biol Chem 1999, 274:19814-19822.
138 Vendrov AE, Madamanchi NR, Hakim ZS, Rojas M, Runge MS:Thrombin and NAD(P)H oxidase-mediated regulation of CD44 and BMP4-Id pathway in VSMC, restenosis, and atherosclerosis. Circ Res 2006,98:1254-1263.
139 Teshigawara K, Ogawa W, Mori T, Matsuki Y, Watanabe E, Hiramatsu R, Inoue H, Miyake K, Sakaue H, Kasuga M:Role of Kruppel-like factor 15 in PEPCK gene expression in the liver. Biochem Biophys Res Commun 2005, 327:920-926.
140 Gray S, Wang B, Orihuela Y, Hong EG, Fisch S, Haldar S, Cline GW, Kim JK, Peroni OD, Kahn BB, Jain MK:Regulation of gluconeogenesis by Kruppel-like factor 15. Cell Metab 2007,5:305-312.
141 Boluyt MO, O'Neill L, Meredith AL, Bing OH, Brooks WW, Conrad CH, Crow MT, Lakatta EG:Alterations in cardiac gene expression during the transition from stable hypertrophy to heart failure. Marked upregulation of genes encoding extracellular matrix components. Circ Res 1994,75:23-32.
142 Dorn GW,2nd, Hahn HS:Genetic factors in cardiac hypertrophy. Ann N Y Acad Sci 2004,1015:225-237.
143 MacLellan WR, Schneider MD:Genetic dissection of cardiac growth control pathways. Annu Rev Physiol 2000,62:289-319.
144 Kawai-Kowase K, Kurabayashi M, Hoshino Y, Ohyama Y, Nagai R: Transcriptional activation of the zinc finger transcription factor BTEB2 gene by Egr-1 through mitogen-activated protein kinase pathways in vascular smooth muscle cells. Circ Res 1999,85:787-795.
145 Olson EN, Schneider MD:Sizing up the heart:development redux in disease. Genes Dev 2003,17:1937-1956.
146 Liang Q, De Windt LJ, Witt SA, Kimball TR, Markham BE, Molkentin JD:The transcription factors GATA4 and GATA6 regulate cardiomyocyte hypertrophy in vitro and in vivo. J Biol Chem 2001,276:30245-30253.
147 van Oort RJ, van Rooij E, Bourajjaj M, Schimmel J, Jansen MA, van der Nagel R, Doevendans PA, Schneider MD, van Echteld CJ, De Windt LJ:MEF2 activates a genetic program promoting chamber dilation and contractile dysfunction in calcineurin-induced heart failure. Circulation 2006, 114:298-308.
148 Fisch S, Gray S, Heymans S, Haldar SM, Wang B, Pfister O, Cui L, Kumar A, Lin Z, Sen-Banerjee S, Das H, Petersen CA, Mende U, Burleigh BA, Zhu Y, Pinto YM, Liao R, Jain MK:Kruppel-like factor 15 is a regulator of cardiomyocyte hypertrophy. Proc Natl Acad Sci U S A 2007,104:7074-7079.
149 Chin MT:KLF15 and cardiac'fibrosis:the heart thickens. JMol Cell Cardiol 2008,45:165-167.
150 Sun Y, Zhang JQ, Zhang J, Lamparter S:Cardiac remodeling by fibrous tissue after infarction in rats. JLab Clin Med 2000,135:316-323.
151 Wang B, Haldar SM, Lu Y, Ibrahim OA, Fisch S, Gray S, Leask A, Jain MK: The Kruppel-like factor KLF15 inhibits connective tissue growth factor (CTGF) expression in cardiac fibroblasts. J Mol Cell Cardiol 2008, 45:193-197.
152 James CG, Ulici V, Tuckermann J, Underhill TM, Beier F:Expression profiling of Dexamethasone-treated primary chondrocytes identifies targets of glucocorticoid signalling in endochondral bone development. BMC Genomics 2007,8:205.
153 Kitamura K, Kangawa K, Kawamoto M, Ichiki Y, Nakamura S, Matsuo H, Eto T:Adrenomedullin:a novel hypotensive peptide isolated from human pheochromocytoma. Biochem Biophys Res Commun 1993,192:553-560.
154 Harmancey R, Senard JM, Rouet P, Pathak A, Smih F:Adrenomedullin inhibits adipogenesis under transcriptional control of insulin. Diabetes 2007, 56:553-563.
155 Nambu T, Arai H, Komatsu Y, Yasoda A, Moriyama K, Kanamoto N, Itoh H, Nakao K:Expression of the adrenomedullin gene in adipose tissue. Regul Pept 2005,132:17-22.
156 Nagare T, Sakaue H, Takashima M, Takahashi K, Gomi H, Matsuki Y, Watanabe E, Hiramatsu R, Ogawa W, Kasuga M:The Kruppel-like factor KLF15 inhibits transcription of the adrenomedullin gene in adipocytes. Biochem Biophys Res Commun 2009,379:98-103.
157 Rosenfield RL:Clinical practice. Hirsutism. N Engl J Med 2005, 353:2578-2588.
158 Du X, Rosenfield RL, Qin K:KLF15 Is a transcriptional regulator of the human 17beta-hydroxysteroid dehydrogenase type 5 gene. A potential link between regulation of testosterone production and fat stores in women. J Clin Endocrinol Metab 2009,94:2594-2601.
159 Gaston K, Jayaraman PS:Transcriptional repression in eukaryotes: repressors and repression mechanisms. Cell Mol Life Sci 2003,60:721-741.
160 Ogata K, Sato K, Tahirov TH:Eukaryotic transcriptional regulatory complexes:cooperativity from near and afar. Curr Opin Struct Biol 2003, 13:40-48.
1 Hey PJ, Twells RC, Phillips MS, Yusuke N, Brown SD, Kawaguchi Y, Cox R, Guochun X, Dugan V, Hammond H, Metzker ML, Todd JA, Hess JF:Cloning of a novel member of the low-density lipoprotein receptor family. Gene 1998,216:103-111.
2 Wehrli M, Dougan ST, Caldwell K, O'Keefe L, Schwartz S, Vaizel-Ohayon D, Schejter E, Tomlinson A, DiNardo S:arrow encodes an LDL-receptor-related protein essential for Wingless signalling. Nature 2000, 407:527-530.
3 Tamai K, Semenov M, Kato Y, Spokony R, Liu C, Katsuyama Y, Hess F, Saint-Jeannet JP, He X:LDL-receptor-related proteins in Wnt signal transduction. Nature 2000,407:530-535.
4 Gong Y, Slee RB, Fukai N, Rawadi G, Roman-Roman S, Reginato AM, Wang H, Cundy T, Glorieux FH, Lev D, Zacharin M, Oexle K, Marcelino J, Suwairi W, Heeger S, Sabatakos G, Apte S, Adkins WN, Allgrove J, Arslan-Kirchner M, Batch JA, Beighton P, Black GC, Boles RG, Boon LM, Borrone C, Brunner HG, Carle GF, Dallapiccola B, De Paepe A, Floege B, Halfliide ML, Hall B, Hennekam RC, Hirose T, Jans A, Juppner H, Kim CA, Keppler-Noreuil K, Kohlschuetter A, LaCombe D, Lambert M, Lemyre E, Letteboer T, Peltonen L, Ramesar RS, Romanengo M, Somer H, Steichen-Gersdorf E, Steinmann B, Sullivan B, Superti-Furga A, Swoboda W, van den Boogaard MJ, Van Hul W, Vikkula M, Votruba M, Zabel B, Garcia T, Baron R, Olsen BR, Warman ML: LDL receptor-related protein 5 (LRP5) affects bone accrual and eye development. Cell 2001,107:513-523.
5 Kato M, Patel MS, Levasseur R, Lobov I, Chang BH, Glass DA,2nd, Hartmann C, Li L, Hwang TH, Brayton CF, Lang RA, Karsenty G, Chan L: Cbfal-independent decrease in osteoblast proliferation, osteopenia, and persistent embryonic eye vascularization in mice deficient in Lrp5, a Wnt coreceptor. J Cell Biol 2002,157:303-314.
6 Boyden LM, Mao J, Belsky J, Mitzner L, Farhi A, Mitnick MA, Wu D, Insogna K, Lifton RP:High bone density due to a mutation in LDL-receptor-related protein 5. N Engl JMed 2002,346:1513-1521.
7 Little RD, Carulli JP, Del Mastro RG, Dupuis J, Osborne M, Folz C, Manning SP, Swain PM, Zhao SC, Eustace B, Lappe MM, Spitzer L, Zweier S, Braunschweiger K, Benchekroun Y, Hu X, Adair R, Chee L, FitzGerald MG, Tulig C, Caruso A, Tzellas N, Bawa A, Franklin B, McGuire S, Nogues X, Gong G, Allen KM, Anisowicz A, Morales AJ, Lomedico PT, Recker SM, Van Eerdewegh P, Recker RR, Johnson ML:A mutation in the LDL receptor-related protein 5 gene results in the autosomal dominant high-bone-mass trait. Am JHum Genet 2002,70:11-19.
8 Van Wesenbeeck L, Cleiren E, Gram J, Beals RK, Benichou O, Scopelliti D, Key L, Renton T, Bartels C, Gong Y, Warman ML, De Vernejoul MC, Bollerslev J, Van Hul W:Six novel missense mutations in the LDL receptor-related protein 5 (LRP5) gene in different conditions with an increased bone density. Am JHum Genet 2003,72:763-771.
9 Babij P, Zhao W, Small C, Kharode Y, Yaworsky PJ, Bouxsein ML, Reddy PS, Bodine PV, Robinson JA, Bhat B, Marzolf J, Moran RA, Bex F:High bone mass in mice expressing a mutant LRP5 gene. J Bone Miner Res 2003, 18:960-974.
10 Urano T, Shiraki M, Ezura Y, Fujita M, Sekine E, Hoshino S, Hosoi T, Orimo H, Emi M, Ouchi Y, Inoue S:Association of a single-nucleotide polymorphism in low-density lipoprotein receptor-related protein 5 gene with bone mineral density. J Bone Miner Metab 2004,22:341-345.
11 Ferrari SL, Deutsch S, Antonarakis SE:Pathogenic mutations and polymorphisms in the lipoprotein receptor-related protein 5 reveal a new biological pathway for the control of bone mass. Curr Opin Lipidol 2005, 16:207-214.
12 Koller DL, Ichikawa S, Johnson ML, Lai D, Xuei X, Edenberg HJ, Conneally PM, Hui SL, Johnston CC, Peacock M, Foroud T, Econs MJ:Contribution of the LRP5 gene to normal variation in peak BMD in women. J Bone Miner Res 2005,20:75-80.
13 Kiel DP, Ferrari SL, Cupples LA, Karasik D, Manen D, Imamovic A, Herbert AG, Dupuis J:Genetic variation at the low-density lipoprotein receptor-related protein 5 (LRP5) locus modulates Wnt signaling and the relationship of physical activity with bone mineral density in men. Bone 2007,40:587-596.
14 Jiao X, Ventruto V, Trese MT, Shastry BS, Hejtmancik JF:Autosomal recessive familial exudative vitreoretinopathy is associated with mutations in LRP5. Am JHum Genet 2004,75:878-884.
15 Qin M, Hayashi H, Oshima K, Tahira T, Hayashi K, Kondo H:Complexity of the genotype-phenotype correlation in familial exudative vitreoretinopathy with mutations in the LRP5 and/or FZD4 genes. Hum Mutat 2005, 26:104-112.
16 Toomes C, Bottomley HM, Jackson RM, Towns KV, Scott S, Mackey DA, Craig JE, Jiang L, Yang Z, Trembath R, Woodruff G, Gregory-Evans CY, Gregory-Evans K, Parker MJ, Black GC, Downey LM, Zhang K, Inglehearn CF: Mutations in LRP5 or FZD4 underlie the common familial exudative vitreoretinopathy locus on chromosome 11q. Am J Hum Genet 2004, 74:721-730.
17 Xu Q, Wang Y, Dabdoub A, Smallwood PM, Williams J, Woods C, Kelley MW, Jiang L, Tasman W, Zhang K, Nathans J:Vascular development in the retina and inner ear:control by Norrin and Frizzled-4, a high-affinity ligand-receptor pair. Cell 2004,116:883-895.
18 Fujino T, Asaba H, Kang MJ, Ikeda Y, Sone H, Takada S, Kim DH, Ioka RX, Ono M, Tomoyori H, Okubo M, Murase T, Kamataki A, Yamamoto J, Magoori K, Takahashi S, Miyamoto Y, Oishi H, Nose M, Okazaki M, Usui S, Imaizumi K, Yanagisawa M, Sakai J, Yamamoto TT:Low-density lipoprotein receptor-related protein 5 (LRP5) is essential for normal cholesterol metabolism and glucose-induced insulin secretion. Proc Natl Acad Sci U S A 2003,100:229-234.
19 Magoori K, Kang MJ, Ito MR, Kakuuchi H, Ioka RX, Kamataki A, Kim DH, Asaba H, Iwasaki S, Takei YA, Sasaki M, Usui S, Okazaki M, Takahashi S, Ono M, Nose M, Sakai J, Fujino T, Yamamoto TT:Severe hypercholesterolemia, impaired fat tolerance, and advanced atherosclerosis in mice lacking both low density lipoprotein receptor-related protein 5 and apolipoprotein E. JBiol Chem 2003,278:11331-11336.
20 Hagen G, Muller S, Beato M, Suske G:Spl-mediated transcriptional activation is repressed by Sp3. Embo J1994,13:3843-3851.
21 Xia Y, Jiang B, Zou Y, Gao G, Shang L, Chen B, Liu Q, Gong Y:Spl and CREB regulate basal transcription of the human SNF2L gene. Biochem Biophys Res Commun 2008,368:438-444.
22 Bieker JJ:Kruppel-like factors:three fingers in many pies. JBiol Chem 2001, 276:34355-34358.
23 Kaczynski J, Cook T, Urrutia R:Spl-and Kruppel-like transcription factors. Genome Biol 2003,4:206.
24 Cook T, Gebelein B, Belal M, Mesa K, Urrutia R:Three conserved transcriptional repressor domains are a defining feature of the TIEG subfamily of Spl-like zinc finger proteins. J Biol Chem 1999, 274:29500-29504.
25 Gray S, Feinberg MW, Hull S, Kuo CT, Watanabe M, Sen-Banerjee S, DePina A, Haspel R, Jain MK:The Kruppel-like factor KLF15 regulates the insulin-sensitive glucose transporter GLUT4. J Biol Chem 2002, 277:34322-34328.
26 Otteson DC, Liu Y, Lai H, Wang C, Gray S, Jain MK, Zack DJ:Kruppel-like factor 15, a zinc-finger transcriptional regulator, represses the rhodopsin and interphotoreceptor retinoid-binding protein promoters. Invest Ophthalmol Vis Sci 2004,45:2522-2530.
27 Uchida S, Tanaka Y, Ito H, Saitoh-Ohara F, Inazawa J, Yokoyama KK, Sasaki S, Marumo F:Transcriptional regulation of the CLC-K1 promoter by myc-associated zinc finger protein and kidney-enriched Kruppel-like factor, a novel zinc finger repressor. Mol Cell Biol 2000,20:7319-7331.
28 Yamamoto J, Ikeda Y, Iguchi H, Fujino T, Tanaka T, Asaba H, Iwasaki S, Ioka RX, Kaneko IW, Magoori K, Takahashi S, Mori T, Sakaue H, Kodama T, Yanagisawa M, Yamamoto TT, Ito S, Sakai J:A Kruppel-like factor KLF15 contributes fasting-induced transcriptional activation of mitochondrial acetyl-CoA synthetase gene AceCS2. J Biol Chem 2004,279:16954-16962.
29 Suske G:The Sp-family of transcription factors. Gene 1999,238:291-300.
30 Philipsen S, Suske G:A tale of three fingers:the family of mammalian Sp/XKLF transcription factors. Nucleic Acids Res 1999,27:2991-3000.
1 Bieker JJ:Kruppel-like factors:three fingers in many pies. J Biol Chem 2001, 276:34355-34358.
2 Black AR, Black JD, Azizkhan-Clifford J:Spl and kruppel-like factor family of transcription factors in cell growth regulation and cancer. J Cell Physiol 2001,188:143-160.
3 Kaczynski J, Cook T, Urrutia R:Spl-and Kruppel-like transcription factors. Genome Biol 2003,4:206.
4 Uchida S, Tanaka Y, Ito H, Saitoh-Ohara F, Inazawa J, Yokoyama KK, Sasaki S, Marumo F: Transcriptional regulation of the CLC-K1 promoter by myc-associated zinc finger protein and kidney-enriched Kruppel-like factor, a novel zinc finger repressor. Mol Cell Biol 2000, 20:7319-7331.
5 Otteson DC, Liu Y, Lai H, Wang C, Gray S, Jain MK, Zack DJ:Kruppel-like factor 15, a zinc-finger transcriptional regulator, represses the rhodopsin and interphotoreceptor retinoid-binding protein promoters. Invest Ophthalmol Vis Sci 2004,45:2522-2530.
6 Gray S, Feinberg MW, Hull S, Kuo CT, Watanabe M, Sen-Banerjee S, DePina A, Haspel R, Jain MK:The Kruppel-like factor KLF15 regulates the insulin-sensitive glucose transporter GLUT4. JBiol Chem 2002,277:34322-34328.
7 Yamamoto J, Ikeda Y, Iguchi H, Fujino T, Tanaka T, Asaba H, Iwasaki S, Ioka RX, Kaneko IW, Magoori K, Takahashi S, Mori T, Sakaue H, Kodama T, Yanagisawa M, Yamamoto TT, Ito S, Sakai J:A Kruppel-like factor KLF15 contributes fasting-induced transcriptional activation of mitochondrial acetyl-CoA synthetase gene AceCS2. J Biol Chem 2004, 279:16954-16962.
8 Mori T, Sakaue H, Iguchi H, Gomi H, Okada Y, Takashima Y, Nakamura K, Nakamura T, Yamauchi T, Kubota N, Kadowaki T, Matsuki Y, Ogawa W, Hiramatsu R, Kasuga M:Role of Kruppel-like factor 15 (KLF15) in transcriptional regulation of adipogenesis. J Biol Chem 2005,280:12867-12875.
9 Fisch S, Gray S, Heymans S, Haldar SM, Wang B, Pfister O, Cui L, Kumar A, Lin Z, Sen-Banerjee S, Das H, Petersen CA, Mende U, Burleigh BA, Zhu Y, Pinto YM, Liao R, Jain MK:Kruppel-like factor 15 is a regulator of cardiomyocyte hypertrophy. Proc Natl Acad Sci USA 2007,104:7074-7079.
10 Gray S, Wang B, Orihuela Y, Hong EG, Fisch S, Haldar S, Cline GW, Kim JK, Peroni OD, Kahn BB, Jain MK:Regulation of gluconeogenesis by Kruppel-like factor 15. Cell Metab 2007, 5:305-312.
11 Teshigawara K, Ogawa W, Mori T, Matsuki Y, Watanabe E, Hiramatsu R, Inoue H, Miyake K, Sakaue H, Kasuga M:Role of Kruppel-like factor 15 in PEPCK gene expression in the liver. Biochem Biophys Res Commun 2005,327:920-926.
12 Xia Y, Jiang B, Zou Y, Gao G, Shang L, Chen B, Liu Q, Gong Y:Spl and CREB regulate basal transcription of the human SNF2L gene. Biochem Biophys Res Commun 2008, 368:438-444.
13 Suske G:The Sp-family of transcription factors. Gene 1999,238:291-300.
14 Philipsen S, Suske G:A tale of three fingers:the family of mammalian Sp/XKLF transcription factors. Nucleic Acids Res 1999,27:2991-3000.
15 Gonzalez GA, Montminy MR:Cyclic AMP stimulates somatostatin gene transcription by phosphorylation of CREB at serine 133. Cell 1989,59:675-680.
16 Viollet B, Lefrancois-Martinez AM, Henrion A, Kahn A, Raymondjean M, Martinez A: Immunochemical characterization and transacting properties of upstream stimulatory factor isoforms. JBiol Chem 1996,271:1405-1415.
17 Gregor PD, Sawadogo M, Roeder RG:The adenovirus major late transcription factor USF is a member of the helix-loop-helix group of regulatory proteins and binds to DNA as a dimer. Genes Dev 1990,4:1730-1740.
18 Sawadogo M, Van Dyke MW, Gregor PD, Roeder RG:Multiple forms of the human gene-specific transcription factor USF. Ⅰ. Complete purification and identification of USF from HeLa cell nuclei. JBiol Chem 1988,263:11985-11993.
19 Sawadogo M:Multiple forms of the human gene-specific transcription factor USF. Ⅱ. DNA binding properties and transcriptional activity of the purified HeLa USF. JBiol Chem 1988, 263:11994-12001.
20 Sirito M, Walker S, Lin Q, Kozlowski MT, Klein WH, Sawadogo M:Members of the USF family of helix-loop-helix proteins bind DNA as homo-as well as heterodimers. Gene Expr 1992,2:231-240.
21 Sirito M, Lin Q, Maity T, Sawadogo M:Ubiquitous expression of the 43-and 44-kDa forms of transcription factor USF in mammalian cells. Nucleic Acids Res 1994,22:427-433.
22 Henrion AA, Martinez A, Mattei MG, Kahn A, Raymondjean M:Structure, sequence, and chromosomal location of the gene for USF2 transcription factors in mouse. Genomics 1995, 25:36-43.
23 Li N, Seetharam B:A 69-base pair fragment derived from human transcobalamin Ⅱ promoter is sufficient for high bidirectional activity in the absence of a TATA box and an initiator element in transfected cells. Role of an E box in transcriptional activity. J Biol Chem 1998,273:28170-28177.
24 Ge Y, Konrad MA, Matherly LH, Taub JW:Transcriptional regulation of the human cystathionine beta-synthase-1b basal promoter:synergistic transactivation by transcription factors NF-Y and Spl/Sp3. Biochem J 2001,357:97-105.
25 Ge Y, Jensen TL, Matherly LH, Taub JW:Physical and functional interactions between USF and Spl proteins regulate human deoxycytidine kinase promoter activity. J Biol Chem 2003, 278:49901-49910.
26 Quinn PG:Distinct activation domains within cAMP response element-binding protein (CREB) mediate basal and cAMP-stimulated transcription. J Biol Chem 1993, 268:16999-17009.
27 Mayr B, Montminy M:Transcriptional regulation by the phosphorylation-dependent factor CREB. Nat Rev Mol Cell Biol 2001,2:599-609.
2 Herz J, Willnow TE:Functions of the LDL receptor gene family. Ann N Y Acad Sci 1994,737:14-19.
3 Brown MS, Herz J, Goldstein JL:LDL-receptor structure. Calcium cages, acid baths and recycling receptors. Nature 1997,388:629-630.
4 Dong Y, Lathrop W, Weaver D, Qiu Q, Cini J, Bertolini D, Chen D:Molecular cloning and characterization of LR3, a novel LDL receptor family protein with mitogenic activity. Biochem Biophys Res Commun 1998,251:784-790.
5 Chen D, Lathrop W, Dong Y:Molecular cloning of mouse Lrp7(Lr3) cDNA and chromosomal mapping of orthologous genes in mouse and human. Genomics 1999,55:314-321.
6 Hey PJ, Twells RC, Phillips MS, Yusuke N, Brown SD, Kawaguchi Y, Cox R, Guochun X, Dugan V, Hammond H, Metzker ML, Todd JA, Hess JF:Cloning of a novel member of the low-density lipoprotein receptor family. Gene 1998,216:103-111.
7 Kato M, Patel MS, Levasseur R, Lobov I, Chang BH, Glass DA,2nd, Hartmann C, Li L, Hwang TH, Brayton CF, Lang RA, Karsenty G, Chan L: Cbfal-independent decrease in osteoblast proliferation, osteopenia, and persistent embryonic eye vascularization in mice deficient in Lrp5, a Wnt coreceptor. J Cell Biol 2002,157:303-314.
8 Figueroa DJ, Hess JF, Ky B, Brown SD, Sandig V, Hermanowski-Vosatka A, Twells RC, Todd JA, Austin CP:Expression of the type I diabetes-associated gene LRP5 in macrophages, vitamin A system cells, and the Islets of Langerhans suggests multiple potential roles in diabetes. J Histochem Cytochem 2000,48:1357-1368.
9 Boyden LM, Mao J, Belsky J, Mitzner L, Farhi A, Mitnick MA, Wu D, Insogna K, Lifton RP:High bone density due to a mutation in LDL-receptor-related protein 5. NEngl JMed 2002,346:1513-1521.
10 Little RD, Carulli JP, Del Mastro RG, Dupuis J, Osborne M, Folz C, Manning SP, Swain PM, Zhao SC, Eustace B, Lappe MM, Spitzer L, Zweier S, Braunschweiger K, Benchekroun Y, Hu X, Adair R, Chee L, FitzGerald MG, Tulig C, Caruso A, Tzellas N, Bawa A, Franklin B, McGuire S, Nogues X, Gong G, Allen KM, Anisowicz A, Morales AJ, Lomedico PT, Recker SM, Van Eerdewegh P, Recker RR, Johnson ML:A mutation in the LDL receptor-related protein 5 gene results in the autosomal dominant high-bone-mass trait. Am JHum Genet 2002,70:11-19.
11 Van Wesenbeeck L, Cleiren E, Gram J, Beals RK, Benichou O, Scopelliti D, Key L, Renton T, Bartels C, Gong Y, Warman ML, De Vernejoul MC, Bollerslev J, Van Hul W:Six novel missense mutations in the LDL receptor-related protein 5 (LRP5) gene in different conditions with an increased bone density. Am J Hum Genet 2003,72:763-771.
12 Gong Y, Slee RB, Fukai N, Rawadi G, Roman-Roman S, Reginato AM, Wang H, Cundy T, Glorieux FH, Lev D, Zacharin M, Oexle K, Marcelino J, Suwairi W, Heeger S, Sabatakos G, Apte S, Adkins WN, Allgrove J, Arslan-Kirchner M, Batch JA, Beighton P, Black GC, Boles RG, Boon LM, Borrone C, Brunner HG, Carle GF, Dallapiccola B, De Paepe A, Floege B, Halfhide ML, Hall B, Hennekam RC, Hirose T, Jans A, Juppner H, Kim CA, Keppler-Noreuil K, Kohlschuetter A, LaCombe D, Lambert M, Lemyre E, Letteboer T, Peltonen L, Ramesar RS, Romanengo M, Somer H, Steichen-Gersdorf E, Steinmann B, Sullivan B, Superti-Furga A, Swoboda W, van den Boogaard MJ, Van Hul W, Vikkula M, Votruba M, Zabel B, Garcia T, Baron R, Olsen BR, Warman ML: LDL receptor-related protein 5 (LRP5) affects bone accrual and eye development. Cell 2001,107:513-523.
13 Jiao X, Ventruto V, Trese MT, Shastry BS, Hejtmancik JF:Autosomal recessive familial exudative vitreoretinopathy is associated with mutations in LRP5. Am J Hum Genet 2004,75:878-884.
14 Qin M, Hayashi H, Oshima K, Tahira T, Hayashi K, Kondo H:Complexity of the genotype-phenotype correlation in familial exudative vitreoretinopathy with mutations in the LRP5 and/or FZD4 genes. Hum Mutat 2005, 26:104-112.
15 Toomes C, Bottomley HM, Jackson RM, Towns KV, Scott S, Mackey DA, Craig JE, Jiang L, Yang Z, Trembath R, Woodruff Q Gregory-Evans CY, Gregory-Evans K, Parker MJ, Black GC, Downey LM, Zhang K, Inglehearn CF: Mutations in LRP5 or FZD4 underlie the common familial exudative vitreoretinopathy locus on chromosome 11 q. Am J Hum Genet 2004, 74:721-730.
16 Haines JL, Schnetz-Boutaud N, Schmidt S, Scott WK, Agarwal A, Postel EA, Olson L, Kenealy SJ, Hauser M, Gilbert JR, Pericak-Vance MA:Functional candidate genes in age-related macular degeneration:significant association with VEGF, VLDLR, and LRP6. Invest Ophthalmol Vis Sci 2006, 47:329-335.
17 Kadonaga JT, Carner KR, Masiarz FR, Tjian R:Isolation of cDNA encoding transcription factor Spl and functional analysis of the DNA binding domain. Cell 1987,51:1079-1090.
18 Briggs MR, Kadonaga JT, Bell SP, Tjian R:Purification and biochemical characterization of the promoter-specific transcription factor, Spl. Science 1986,234:47-52.
19 Letovsky J, Dynan WS:Measurement of the binding of transcription factor Spl to a single GC box recognition sequence. Nucleic Acids Res 1989, 17:2639-2653.
20 Dunah AW, Jeong H, Griffin A, Kim YM, Standaert DG, Hersch SM, Mouradian MM, Young AB, Tanese N, Krainc D:Spl and TAFII130 transcriptional activity disrupted in early Huntington's disease. Science 2002, 296:2238-2243.
21 Torigoe T, Izumi H, Yoshida Y, Ishiguchi H, Okamoto T, Itoh H, Kohno K:Low pH enhances Spl DNA binding activity and interaction with TBP. Nucleic Acids Res 2003,31:4523-4530.
22 Marin M, Karis A, Visser P, Grosveld F, Philipsen S:Transcription factor Spl is essential for early embryonic development but dispensable for cell growth and differentiation. Cell 1997,89:619-628.
23 Black AR, Black JD, Azizkhan-Clifford J:Spl and kruppel-like factor family of transcription factors in cell growth regulation and cancer. J Cell Physiol 2001,188:143-160.
24 Bieker JJ:Kruppel-like factors:three fingers in many pies. JBiol Chem 2001, 276:34355-34358.
25 Kaczynski J, Cook T, Urrutia R:Spl-and Kruppel-like transcription factors. Genome Biol 2003,4:206.
26 Cook T, Gebelein B, Belal M, Mesa K, Urrutia R:Three conserved transcriptional repressor domains are a defining feature of the TIEG subfamily of Spl-like zinc finger proteins. J Biol Chem 1999, 274:29500-29504.
27 Gray S, Feinberg MW, Hull S, Kuo CT, Watanabe M, Sen-Banerjee S, DePina A, Haspel R, Jain MK:The Kruppel-like factor KLF15 regulates the insulin-sensitive glucose transporter GLUT4. J Biol Chem 2002, 277:34322-34328.
28 Otteson DC, Liu Y, Lai H, Wang C, Gray S, Jain MK, Zack DJ:Kruppel-like factor 15, a zinc-finger transcriptional regulator, represses the rhodopsin and interphotoreceptor retinoid-binding protein promoters. Invest Ophthalmol Vis Sci 2004,45:2522-2530.
29 Uchida S, Tanaka Y, Ito H, Saitoh-Ohara F, Inazawa J, Yokoyama KK, Sasaki S, Marumo F:Transcriptional regulation of the CLC-K1 promoter by myc-associated zinc finger protein and kidney-enriched Kruppel-like factor, a novel zinc finger repressor. Mol Cell Biol 2000,20:7319-7331.
30 Yamamoto J, Ikeda Y, Iguchi H, Fujino T, Tanaka T, Asaba H, Iwasaki S, Ioka RX, Kaneko IW, Magoori K, Takahashi S, Mori T, Sakaue H, Kodama T, Yanagisawa M, Yamamoto TT, Ito S, Sakai J:A Kruppel-like factor KLF15 contributes fasting-induced transcriptional activation of mitochondrial acetyl-CoA synthetase gene AceCS2. JBiol Chem 2004,279:16954-16962.
31 Katagiri T, Yamaguchi A, Komaki M, Abe E, Takahashi N, Ikeda T, Rosen V, Wozney JM, Fujisawa-Sehara A, Suda T:Bone morphogenetic protein-2 converts the differentiation pathway of C2C12 myoblasts into the osteoblast lineage. J Cell Biol 1994,127:1755-1766.
32 Johnson ML:The high bone mass family-the role of Wnt/Lrp5 signaling in the regulation of bone mass. J Musculoskelet Neuronal Interact 2004, 4:135-138.
33 Grimaldi PA, Teboul L, Inadera H, Gaillard D, Amri EZ:Trans-differentiation of myoblasts to adipoblasts:triggering effects of fatty acids and thiazolidinediones. Prostaglandins Leukot Essent Fatty Acids 1997,57:71-75.
34 Tontonoz P, Hu E, Spiegelman BM:Stimulation of adipogenesis in fibroblasts by PPAR gamma 2, a lipid-activated transcription factor. Cell 1994, 79:1147-1156.
35 De Coppi P, Milan G, Scarda A, Boldrin L, Centobene C, Piccoli M, Pozzobon M, Pilon C, Pagano C, Gamba P, Vettor R:Rosiglitazone modifies the adipogenic potential of human muscle satellite cells. Diabetologia 2006, 49:1962-1973.
36 Uchida S, Rai T, Yatsushige H, Matsumura Y, Kawasaki M, Sasaki S, Marumo F: Isolation and characterization of kidney-specific ClC-K1 chloride channel gene promoter. Am JPhysiol 1998,274:F602-610.
37 Rai T, Uchida S, Sasaki S, Marumo F:Isolation and characterization of kidney-specific CLC-K2 chloride channel gene promoter. Biochem Biophys Res Commun 1999,261:432-438.
38 Nakamura T, Alder H, Gu Y, Prasad R, Canaani O, Kamada N, Gale RP, Lange B, Crist WM, Nowell PC, et al.:Genes on chromosomes 4,9, and 19 involved in 11q23 abnormalities in acute leukemia share sequence homology and/or common motifs. Proc Natl Acad Sci USA 1993,90:4631-4635.
39 Licht JD, Grossel MJ, Figge J, Hansen UM:Drosophila Kruppel protein is a transcriptional repressor. Nature 1990,346:76-79.
40 Madden SL, Cook DM, Rauscher FJ,3rd:A structure-function analysis of transcriptional repression mediated by the WT1, Wilms'tumor suppressor protein. Oncogene 1993,8:1713-1720.
41 Witzgall R, O'Leary E, Leaf A, Onaldi D, Bonventre JV:The Kruppel-associated box-A (KRAB-A) domain of zinc finger proteins mediates transcriptional repression. Proc Natl Acad Sci U S A 1994, 91:4514-4518.
42 Saha S, Brickman JM, Lehming N, Ptashne M:New eukaryotic transcriptional repressors. Nature 1993,363:648-652.
43 Woods A, James CG, Wang G, Dupuis H, Beier F:Control of Chondrocyte Gene Expression by Actin Dynamics:A Novel Role of Cholesterol/Roralpha Signaling in Endochondral Bone Growth. J Cell Mol Med 2009.
44 Otteson DC, Lai H, Liu Y, Zack DJ:Zinc-finger domains of the transcriptional repressor KLF15 bind multiple sites in rhodopsin and IRBP promoters including the CRS-1 and G-rich repressor elements. BMC Mol Biol 2005,6:15.
45 Suske G:The Sp-family of transcription factors. Gene 1999,238:291-300.
46 Viollet B, Lefrancois-Martinez AM, Henrion A, Kahn A, Raymondjean M, Martinez A:Immunochemical characterization and transacting properties of upstream stimulatory factor isoforms. J Biol Chem 1996,271:1405-1415.
47 Gregor PD, Sawadogo M, Roeder RG:The adenovirus major late transcription factor USF is a member of the helix-loop-helix group of regulatory proteins and binds to DNA as a dimer. Genes Dev 1990, 4:1730-1740.
48 Sawadogo M:Multiple forms of the human gene-specific transcription factor USF. Ⅱ. DNA binding properties and transcriptional activity of the purified HeLa USF. JBiol Chem 1988,263:11994-12001.
49 Sawadogo M, Van Dyke MW, Gregor PD, Roeder RG:Multiple forms of the human gene-specific transcription factor USF. Ⅰ. Complete purification and identification of USF from HeLa cell nuclei. J Biol Chem 1988, 263:11985-11993.
50 Shieh BH, Sparkes RS, Gaynor RB, Lusis AJ:Localization of the gene-encoding upstream stimulatory factor (USF) to human chromosome 1q22-q23. Genomics 1993,16:266-268.
51 Groenen PM, Garcia E, Debeer P, Devriendt K, Fryns JP, Van de Ven WJ: Structure, sequence, and chromosome 19 localization of human USF2 and its rearrangement in a patient with multicystic renal dysplasia. Genomics 1996,38:141-148.
52 Sirito M, Lin Q, Maity T, Sawadogo M:Ubiquitous expression of the 43-and 44-kDa forms of transcription factor USF in mammalian cells. Nucleic Acids Res 1994,22:427-433.
53 Sirito M, Walker S, Lin Q, Kozlowski MT, Klein WH, Sawadogo M:Members of the USF family of helix-loop-helix proteins bind DNA as homo-as well as heterodimers. Gene Expr 1992,2:231-240.
54 Virolle T, Coraux C, Ferrigno O, Cailleteau L, Ortonne JP, Pognonec P, Aberdam D:Binding of USF to a non-canonical E-box following stress results in a cell-specific derepression of the lama3 gene. Nucleic Acids Res 2002,30:1789-1798.
55 Ge Y, Jensen TL, Matherly LH, Taub JW:Physical and functional interactions between USF and Spl proteins regulate human deoxycytidine kinase promoter activity. J Biol Chem 2003,278:49901-49910.
56 Coulson JM, Edgson JL, Marshall-Jones ZV, Mulgrew R, Quinn JP, Woll PJ: Upstream stimulatory factor activates the vasopressin promoter via multiple motifs, including a non-canonical E-box. Biochem J 2003, 369:549-561.
57 Pawar SA, Szentirmay MN, Hermeking H, Sawadogo M:Evidence for a cancer-specific switch at the CDK4 promoter with loss of control by both USF and c-Myc. Oncogene 2004,23:6125-6135.
58 Galibert MD, Carreira S, Goding CR:The Usf-1 transcription factor is a novel target for the stress-responsive p38 kinase and mediates UV-induced Tyrosinase expression. Embo J2001,20:5022-5031.
59 Henrion AA, Martinez A, Mattei MG, Kahn A, Raymondjean M:Structure, sequence, and chromosomal location of the gene for USF2 transcription factors in mouse. Genomics 1995,25:36-43.
60 Li N, Seetharam B:A 69-base pair fragment derived from human transcobalamin Ⅱ promoter is sufficient for high bidirectional activity in the absence of a TATA box and an initiator element in transfected cells. Role of an E box in transcriptional activity. J Biol Chem 1998, 273:28170-28177.
61 Ge Y, Konrad MA, Matherly LH, Taub JW:Transcriptional regulation of the human cystathionine beta-synthase-lb basal promoter:synergistic transactivation by transcription factors NF-Y and Spl/Sp3. Biochem J 2001, 357:97-105.
62 Brown MS, Goldstein JL:Receptor-mediated endocytosis:insights from the lipoprotein receptor system. Proc Natl Acad Sci USA 1979,76:3330-3337.
63 Sakai J, Hoshino A, Takahashi S, Miura Y, Ishii H, Suzuki H, Kawarabayasi Y, Yamamoto T:Structure, chromosome location, and expression of the human very low density lipoprotein receptor gene. J Biol Chem 1994, 269:2173-2182.
64 Herz J, Hamann U, Rogne S, Myklebost O, Gausepohl H, Stanley KK:Surface location and high affinity for calcium of a 500-kd liver membrane protein closely related to the LDL-receptor suggest a physiological role as lipoprotein receptor. Embo J1988,7:4119-4127.
65 Liu CX, Musco S, Lisitsina NM, Forgacs E, Minna JD, Lisitsyn NA:LRP-DIT, a putative endocytic receptor gene, is frequently inactivated in non-small cell lung cancer cell lines. Cancer Res 2000,60:1961-1967.
66 Ishii H, Kim DH, Fujita T, Endo Y, Saeki S, Yamamoto TT:cDNA cloning of a new low-density lipoprotein receptor-related protein and mapping of its gene (LRP3) to chromosome bands 19q12-q13.2. Genomics 1998, 51:132-135.
67 Tomita Y, Kim DH, Magoori K, Fujino T, Yamamoto TT:A novel low-density lipoprotein receptor-related protein with type II membrane protein-like structure is abundant in heart. J Biochem 1998,124:784-789.
68 Brown SD, Twells RC, Hey PJ, Cox RD, Levy ER, Soderman AR, Metzker ML, Caskey CT, Todd JA, Hess JF:Isolation and characterization of LRP6, a novel member of the low density lipoprotein receptor gene family. Biochem Biophys Res Commun 1998,248:879-888.
69 Hjalm G, Murray E, Crumley G, Harazim W, Lundgren S, Onyango I, Ek B, Larsson M, Juhlin C, Hellman P, Davis H, Akerstrom G, Rask L, Morse B: Cloning and sequencing of human gp330, a Ca(2+)-binding receptor with potential intracellular signaling properties. Eur J Biochem 1996, 239:132-137.
70 Kim DH, Iijima H, Goto K, Sakai J, Ishii H, Kim HJ, Suzuki H, Kondo H, Saeki S, Yamamoto T:Human apolipoprotein E receptor 2. A novel lipoprotein receptor of the low density lipoprotein receptor family predominantly expressed in brain. J Biol Chem 1996,271:8373-8380.
71 Jacobsen L, Madsen P, Moestrup SK, Lund AH, Tommerup N, Nykjaer A, Sottrup-Jensen L, Gliemann J, Petersen CM:Molecular characterization of a novel human hybrid-type receptor that binds the alpha2-macroglobulin receptor-associated protein. JBiol Chem 1996,271:31379-31383.
72 Doubleday AF, Kaestle FA, Cox LA, Birnbaum S, Mahaney MC, Havill LM: LRP5 sequence and polymorphisms in the baboon. J Med Primatol 2009, 38:97-106.
73 Gliemann J:Receptors of the low density lipoprotein (LDL) receptor family in man. Multiple functions of the large family members via interaction with complex ligands. Biol Chem 1998,379:951-964.
74 Somer H, Palotie A, Somer M, Hoikka V, Peltonen L: Osteoporosis-pseudoglioma syndrome:clinical, morphological, and biochemical studies. JMed Genet 1988,25:543-549.
75 De Paepe A, Leroy JG, Nuytinck L, Meire F, Capoen J: Osteoporosis-pseudoglioma syndrome. Am JMed Genet 1993,45:30-37.
76 Johnson ML, Gong G, Kimberling W, Recker SM, Kimmel DB, Recker RB: Linkage of a gene causing high bone mass to human chromosome 11 (11q12-13). Am J Hum Genet 1997,60:1326-1332.
77 Mizuguchi T, Furuta I, Watanabe Y, Tsukamoto K, Tomita H, Tsujihata M, Ohta T, Kishino T, Matsumoto N, Minakami H, Niikawa N, Yoshiura K:LRP5, low-density-lipoprotein-receptor-related protein 5, is a determinant for bone mineral density. JHum Genet 2004,49:80-86.
78 Ezura Y, Nakajima T, Urano T, Sudo Y, Kajita M, Yoshida H, Suzuki T, Hosoi T, Inoue S, Shiraki M, Emi M:Association of a single-nucleotide variation (A1330V) in the low-density lipoprotein receptor-related protein 5 gene (LRP5) with bone mineral density in adult Japanese women. Bone 2007, 40:997-1005.
79 Balemans W, Van Hul W:The genetics of low-density lipoprotein receptor-related protein 5 in bone:a story of extremes. Endocrinology 2007, 148:2622-2629.
80 Richards JB, Rivadeneira F, Inouye M, Pastinen TM, Soranzo N, Wilson SG, Andrew T, Falchi M, Gwilliam R, Ahmadi KR, Valdes AM, Arp P, Whittaker P, Verlaan DJ, Jhamai M, Kumanduri V, Moorhouse M, van Meurs JB, Hofrnan A, Pols HA, Hart D, Zhai G, Kato BS, Mullin BH, Zhang F, Deloukas P, Uitterlinden AG, Spector TD:Bone mineral density, osteoporosis, and osteoporotic fractures:a genome-wide association study. Lancet 2008, 371:1505-1512.
81 Urano T, Shiraki M, Ezura Y, Fujita M, Sekine E, Hoshino S, Hosoi T, Orimo H, Emi M, Ouchi Y, Inoue S:Association of a single-nucleotide polymorphism in low-density lipoprotein receptor-related protein 5 gene with bone mineral density. J Bone Miner Metab 2004,22:341-345.
82 Ferrari SL, Deutsch S, Choudhury U, Chevalley T, Bonjour JP, Dermitzakis ET, Rizzoli R, Antonarakis SE:Polymorphisms in the low-density lipoprotein receptor-related protein 5 (LRP5) gene are associated with variation in vertebral bone mass, vertebral bone size, and stature in whites. Am J Hum Genet 2004,74:866-875.
83 Koh JM, Jung MH, Hong JS, Park HJ, Chang JS, Shin HD, Kim SY, Kim GS: Association between bone mineral density and LDL receptor-related protein 5 gene polymorphisms in young Korean men. J Korean Med Sci 2004,19:407-412.
84 Lau HH, Ng MY, Ho AY, Luk KD, Kung AW:Genetic and environmental determinants of bone mineral density in Chinese women. Bone 2005, 36:700-709.
85 Zhang ZL, Qin YJ, He JW, Huang QR, Li M, Hu YQ, Liu YJ:Association of polymorphisms in low-density lipoprotein receptor-related protein 5 gene with bone mineral density in postmenopausal Chinese women. Acta Pharmacol Sin 2005,26:1111-1116.
86 Lau HH, Ng MY, Cheung WM, Paterson AD, Sham PC, Luk KD, Chan V, Kung AW:Assessment of linkage and association of 13 genetic loci with bone mineral density. JBone Miner Metab 2006,24:226-234.
87 Urano T, Shiraki M, Narusawa K, Usui T, Sasaki N, Hosoi T, Ouchi Y, Nakamura T, Inoue S:Q89R polymorphism in the LDL receptor-related protein 5 gene is associated with spinal osteoarthritis in postmenopausal Japanese women. Spine (Phila Pa 1976) 2007,32:25-29.
88 Urano T:[Regulation of bone metabolism by pathogenic mutations and polymorphism in the LRP5-Wnt signaling genes]. Nippon Rinsho 2007,65 Suppl 9:95-100.
89 Urano T, Shiraki M, Usui T, Sasaki N, Ouchi Y, Inoue S:A1330V variant of the low-density lipoprotein receptor-related protein 5 (LRP5) gene decreases Wnt signaling and affects the total body bone mineral density in Japanese women. Endocr J 2009,56:625-631.
90 Koay MA, Tobias JH, Leary SD, Steer CD, Vilarino-Guell C, Brown MA:The effect of LRP5 polymorphisms on bone mineral density is apparent in childhood. Calcif Tissue Int 2007,81:1-9.
91 Utriainen P, Jaaskelainen J, Saarinen A, Vanninen E, Makitie O, Voutilainen R: Body Composition and Bone Mineral Density in Children with Premature Adrenarche and the Association of LRP5 Gene Polymorphisms with Bone Mineral Density. J Clin Endocrinol Metab 2009.
92 Li Y, Bu G:LRP5, a multifunctional cell surface receptor. Curr Opin Lipidol 2004,15:361-363.
93 Tamai K, Semenov M, Kato Y, Spokony R, Liu C, Katsuyama Y, Hess F, Saint-Jeannet JP, He X:LDL-receptor-related proteins in Wnt signal transduction. Nature 2000,407:530-535.
94 He X, Semenov M, Tamai K, Zeng X:LDL receptor-related proteins 5 and 6 in Wnt/beta-catenin signaling:arrows point the way. Development 2004, 131:1663-1677.
95 Moon RT, Kohn AD, De Ferrari GV, Kaykas A:WNT and beta-catenin signalling:diseases and therapies. Nat Rev Genet 2004,5:691-701.
96 Glass DA,2nd, Bialek P, Ahn JD, Starbuck M, Patel MS, Clevers H, Taketo MM, Long F, McMahon AP, Lang RA, Karsenty G:Canonical Wnt signaling in differentiated osteoblasts controls osteoclast differentiation. Dev Cell 2005,8:751-764.
97 Boonstra FN, van Nouhuys CE, Schuil J, de Wijs IJ, van der Donk KP, Nikopoulos K, Mukhopadhyay A, Scheffer H, Tilanus MA, Cremers FP, Hoefsloot LH:Clinical and molecular evaluation of probands and family members with familial exudative vitreoretinopathy. Invest Ophthalmol Vis Sci 2009,50:4379-4385.
98 Ito M, Yoshioka M:Regression of the hyaloid vessels and pupillary membrane of the mouse. Anat Embryol (Berl) 1999,200:403-411.
99 Xu Q, Wang Y, Dabdoub A, Smallwood PM, Williams J, Woods C, Kelley MW, Jiang L, Tasman W, Zhang K, Nathans J:Vascular development in the retina and inner ear:control by Norrin and Frizzled-4, a high-affinity ligand-receptor pair. Cell 2004,116:883-895.
100 Pinson KI, Brennan J, Monkley S, Avery BJ, Skarnes WC:An LDL-receptor-related protein mediates Wnt signalling in mice. Nature 2000, 407:535-538.
101 Xia CH, Liu H, Cheung D, Wang M, Cheng C, Du X, Chang B, Beutler B, Gong X:A model for familial exudative vitreoretinopathy caused by LPR5 mutations. Hum Mol Genet 2008,17:1605-1612.
102 Lang RA, Bishop JM:Macrophages are required for cell death and tissue remodeling in the developing mouse eye. Cell 1993,74:453-462.
103 Lang RA:Apoptosis in mammalian eye development:lens morphogenesis, vascular regression and immune privilege. Cell Death Differ 1997,4:12-20.
104 Fujino T, Asaba H, Kang MJ, Ikeda Y, Sone H, Takada S, Kim DH, Ioka RX, Ono M, Tomoyori H, Okubo M, Murase T, Kamataki A, Yamamoto J, Magoori K, Takahashi S, Miyamoto Y, Oishi H, Nose M, Okazaki M, Usui S, Imaizumi K, Yanagisawa M, Sakai J, Yamamoto TT:Low-density lipoprotein receptor-related protein 5 (LRP5) is essential for normal cholesterol metabolism and glucose-induced insulin secretion. Proc Natl Acad Sci U S A 2003,100:229-234.
105 Suwazono Y, Kobayashi E, Dochi M, Miura K, Morikawa Y, Ishizaki M, Kido T, Nakagawa H, Nogawa K:Combination of the C1429T polymorphism in the G-protein beta-3 subunit gene and the A1330V polymorphism in the low-density lipoprotein receptor-related protein 5 gene is a risk factor for hypercholesterolaemia. Clin Exp Med 2007,7:108-114.
106 Zenibayashi M, Miyake K, Horikawa Y, Hirota Y, Teranishi T, Kouyama K, Sakaguchi K, Takeda J, Kasuga M:Lack of association of LRP5 and LRP6 polymorphisms with type 2 diabetes mellitus in the Japanese population. Endocr J2008,55:699-707.
107 Bieker JJ:Isolation, genomic structure, and expression of human erythroid Kruppel-like factor (EKLF). DNA Cell Biol 1996,15:347-352.
108 Anderson KP, Kern CB, Crable SC, Lingrel JB:Isolation of a gene encoding a functional zinc finger protein homologous to erythroid Kruppel-like factor: identification of a new multigene family. Mol Cell Biol 1995,15:5957-5965.
109 Suske G, Bruford E, Philipsen S:Mammalian SP/KLF transcription factors: bring in the family. Genomics 2005,85:551-556.
110 Shields JM, Christy RJ, Yang VW:Identification and characterization of a gene encoding a gut-enriched Kruppel-like factor expressed during growth arrest. J Biol Chem 1996,271:20009-20017.
111 Koritschoner NP, Bocco JL, Panzetta-Dutari Gm, Dumur CI, Flury A, Patrito LC:A novel human zinc finger protein that interacts with the core promoter element of a TATA box-less gene. J Biol Chem 1997, 272:9573-9580.
112 Matsumoto N, Laub F, Aldabe R, Zhang W, Ramirez F, Yoshida T, Terada M: Cloning the cDNA for a new human zinc finger protein defines a group of closely related Kruppel-like transcription factors. J Biol Chem 1998, 273:28229-28237.
113 van Vliet J, Turner J, Crossley M:Human Kruppel-like factor 8:a CACCC-box binding protein that associates with CtBP and represses transcription. Nucleic Acids Res 2000,28:1955-1962.
114 Ohe N, Yamasaki Y, Sogawa K, Inazawa J, Ariyama T, Oshimura M, Fujii-Kuriyama Y:Chromosomal localization and cDNA sequence of human BTEB, a GC box binding protein. Somat Cell Mol Genet 1993,19:499-503.
115 Tachibana I, Imoto M, Adjei PN, Gores GJ, Subramaniam M, Spelsberg TC, Urrutia R:Overexpression of the TGFbeta-regulated zinc finger encoding gene, TIEG, induces apoptosis in pancreatic epithelial cells. J Clin Invest 1997,99:2365-2374.
116 Asano H, Li XS, Stamatoyannopoulos G:FKLF, a novel Kruppel-like factor that activates human embryonic and fetal beta-like globin genes. Mol Cell Biol 1999,19:3571-3579.
117 Imhof A, Schuierer M, Werner O, Moser M, Roth C, Bauer R, Buettner R: Transcriptional regulation of the AP-2alpha promoter by BTEB-1 and AP-2rep, a novel wt-1/egr-related zinc finger repressor. Mol Cell Biol 1999, 19:194-204.
118 Scohy S, Gabant P, Van Reeth T, Hertveldt V, Dreze PL, Van Vooren P, Riviere M, Szpirer J, Szpirer C:Identification of KLF13 and KLF14 (SP6), novel members of the SP/XKLF transcription factor family. Genomics 2000, 70:93-101.
119 van Vliet J, Crofts LA, Quinlan KG, Czolij R, Perkins AC, Crossley M:Human KLF17 is a new member of the Sp/KLF family of transcription factors. Genomics 2006,87:474-482.
120 Nuez B, Michalovich D, Bygrave A, Ploemacher R, Grosveld F:Defective haematopoiesis in fetal liver resulting from inactivation of the EKLF gene. Nature 1995,375:316-318.
121 Kuo CT, Veselits ML, Leiden JM:LKLF:A transcriptional regulator of single-positive T cell quiescence and survival. Science 1997,277:1986-1990.
122 Kuo CT, Veselits ML, Barton KP, Lu MM, Clendenin C, Leiden JM:The LKLF transcription factor is required for normal tunica media formation and blood vessel stabilization during murine embryogenesis. Genes Dev 1997,11:2996-3006.
123 Cline GW, Petersen KF, Krssak M, Shen J, Hundal RS, Trajanoski Z, Inzucchi S, Dresner A, Rothman DL, Shulman GI:Impaired glucose transport as a cause of decreased insulin-stimulated muscle glycogen synthesis in type 2 diabetes.
NEngl JMed 1999,341:240-246.
124 Zisman A, Peroni OD, Abel ED, Michael MD, Mauvais-Jarvis F, Lowell BB, Wojtaszewski JF, Hirshman MF, Virkamaki A, Goodyear LJ, Kahn CR, Kahn BB:Targeted disruption of the glucose transporter 4 selectively in muscle causes insulin resistance and glucose intolerance. Nat Med 2000,6:924-928.
125 Abel ED, Peroni O, Kim JK, Kim YB, Boss O, Hadro E, Minnemann T, Shulman GI, Kahn BB:Adipose-selective targeting of the GLUT4 gene impairs insulin action in muscle and liver. Nature 2001,409:729-733.
126 Hauswirth WW, Langerijt AV, Timmers AM, Adamus G, Ulshafer RJ:Early expression and localization of rhodopsin and interphotoreceptor retinoid-binding protein (IRBP) in the developing fetal bovine retina. Exp Eye Res 1992,54:661-670.
127 Araki M, Taketani S:A PCR analysis of rhodopsin gene transcription in rat pineal photoreceptor differentiation. Brain Res Dev Brain Res 1992, 69:149-152.
128 Blackshaw S, Snyder SH:Developmental expression pattern of phototransduction components in mammalian pineal implies a light-sensing function. JNeurosci 1997,17:8074-8082.
129 Sohocki MM, Daiger SP, Bowne SJ, Rodriquez JA, Northrup H, Heckenlively JR, Birch DG, Mintz-Hittner H, Ruiz RS, Lewis RA, Saperstein DA, Sullivan LS:Prevalence of mutations causing retinitis pigmentosa and other inherited retinopathies. Hum Mutat 2001,17:42-51.
130 Lane MD, Tang QQ, Jiang MS:Role of the CCAAT enhancer binding proteins (C/EBPs) in adipocyte differentiation. Biochem Biophys Res Commun 1999,266:677-683.
131 Zhang JW, Tang QQ, Vinson C, Lane MD:Dominant-negative C/EBP disrupts mitotic clonal expansion and differentiation of 3T3-L1 preadipocytes. Proc Natl Acad Sci USA 2004,101:43-47.
132 Mori T, Sakaue H, Iguchi H, Gomi H, Okada Y, Takashima Y, Nakamura K, Nakamura T, Yamauchi T, Kubota N, Kadowaki T, Matsuki Y, Ogawa W, Hiramatsu R, Kasuga M:Role of Kruppel-like factor 15 (KLF15) in transcriptional regulation of adipogenesis. J Biol Chem 2005, 280:12867-12875:
133 Yeh WC, Cao Z, Classon M, McKnight SL:Cascade regulation of terminal adipocyte differentiation by three members of the C/EBP family of leucine zipper proteins. Genes Dev 1995,9:168-181.
134 Wu Z, Bucher NL, Farmer SR:Induction of peroxisome proliferator-activated receptor gamma during the conversion of 3T3 fibroblasts into adipocytes is mediated by C/EBPbeta, C/EBPdelta, and glucocorticoids. Mol Cell Biol 1996,16:4128-4136.
135 Griendling KK, Sorescu D, Ushio-Fukai M:NAD(P)H oxidase:role in cardiovascular biology and disease. Circ Res 2000,86:494-501.
136 Barry-Lane PA, Patterson C, van der Merwe M, Hu Z, Holland SM, Yeh ET, Runge MS:p47phox is required for atherosclerotic lesion progression in ApoE(-/-) mice. JClin Invest 2001,108:1513-1522.
137 Patterson C, Ruef J, Madamanchi NR, Barry-Lane P, Hu Z, Horaist C, Ballinger CA, Brasier AR, Bode C, Runge MS:Stimulation of a vascular smooth muscle cell NAD(P)H oxidase by thrombin. Evidence that p47(phox) may participate in forming this oxidase in vitro and in vivo. J Biol Chem 1999, 274:19814-19822.
138 Vendrov AE, Madamanchi NR, Hakim ZS, Rojas M, Runge MS:Thrombin and NAD(P)H oxidase-mediated regulation of CD44 and BMP4-Id pathway in VSMC, restenosis, and atherosclerosis. Circ Res 2006,98:1254-1263.
139 Teshigawara K, Ogawa W, Mori T, Matsuki Y, Watanabe E, Hiramatsu R, Inoue H, Miyake K, Sakaue H, Kasuga M:Role of Kruppel-like factor 15 in PEPCK gene expression in the liver. Biochem Biophys Res Commun 2005, 327:920-926.
140 Gray S, Wang B, Orihuela Y, Hong EG, Fisch S, Haldar S, Cline GW, Kim JK, Peroni OD, Kahn BB, Jain MK:Regulation of gluconeogenesis by Kruppel-like factor 15. Cell Metab 2007,5:305-312.
141 Boluyt MO, O'Neill L, Meredith AL, Bing OH, Brooks WW, Conrad CH, Crow MT, Lakatta EG:Alterations in cardiac gene expression during the transition from stable hypertrophy to heart failure. Marked upregulation of genes encoding extracellular matrix components. Circ Res 1994,75:23-32.
142 Dorn GW,2nd, Hahn HS:Genetic factors in cardiac hypertrophy. Ann N Y Acad Sci 2004,1015:225-237.
143 MacLellan WR, Schneider MD:Genetic dissection of cardiac growth control pathways. Annu Rev Physiol 2000,62:289-319.
144 Kawai-Kowase K, Kurabayashi M, Hoshino Y, Ohyama Y, Nagai R: Transcriptional activation of the zinc finger transcription factor BTEB2 gene by Egr-1 through mitogen-activated protein kinase pathways in vascular smooth muscle cells. Circ Res 1999,85:787-795.
145 Olson EN, Schneider MD:Sizing up the heart:development redux in disease. Genes Dev 2003,17:1937-1956.
146 Liang Q, De Windt LJ, Witt SA, Kimball TR, Markham BE, Molkentin JD:The transcription factors GATA4 and GATA6 regulate cardiomyocyte hypertrophy in vitro and in vivo. J Biol Chem 2001,276:30245-30253.
147 van Oort RJ, van Rooij E, Bourajjaj M, Schimmel J, Jansen MA, van der Nagel R, Doevendans PA, Schneider MD, van Echteld CJ, De Windt LJ:MEF2 activates a genetic program promoting chamber dilation and contractile dysfunction in calcineurin-induced heart failure. Circulation 2006, 114:298-308.
148 Fisch S, Gray S, Heymans S, Haldar SM, Wang B, Pfister O, Cui L, Kumar A, Lin Z, Sen-Banerjee S, Das H, Petersen CA, Mende U, Burleigh BA, Zhu Y, Pinto YM, Liao R, Jain MK:Kruppel-like factor 15 is a regulator of cardiomyocyte hypertrophy. Proc Natl Acad Sci U S A 2007,104:7074-7079.
149 Chin MT:KLF15 and cardiac'fibrosis:the heart thickens. JMol Cell Cardiol 2008,45:165-167.
150 Sun Y, Zhang JQ, Zhang J, Lamparter S:Cardiac remodeling by fibrous tissue after infarction in rats. JLab Clin Med 2000,135:316-323.
151 Wang B, Haldar SM, Lu Y, Ibrahim OA, Fisch S, Gray S, Leask A, Jain MK: The Kruppel-like factor KLF15 inhibits connective tissue growth factor (CTGF) expression in cardiac fibroblasts. J Mol Cell Cardiol 2008, 45:193-197.
152 James CG, Ulici V, Tuckermann J, Underhill TM, Beier F:Expression profiling of Dexamethasone-treated primary chondrocytes identifies targets of glucocorticoid signalling in endochondral bone development. BMC Genomics 2007,8:205.
153 Kitamura K, Kangawa K, Kawamoto M, Ichiki Y, Nakamura S, Matsuo H, Eto T:Adrenomedullin:a novel hypotensive peptide isolated from human pheochromocytoma. Biochem Biophys Res Commun 1993,192:553-560.
154 Harmancey R, Senard JM, Rouet P, Pathak A, Smih F:Adrenomedullin inhibits adipogenesis under transcriptional control of insulin. Diabetes 2007, 56:553-563.
155 Nambu T, Arai H, Komatsu Y, Yasoda A, Moriyama K, Kanamoto N, Itoh H, Nakao K:Expression of the adrenomedullin gene in adipose tissue. Regul Pept 2005,132:17-22.
156 Nagare T, Sakaue H, Takashima M, Takahashi K, Gomi H, Matsuki Y, Watanabe E, Hiramatsu R, Ogawa W, Kasuga M:The Kruppel-like factor KLF15 inhibits transcription of the adrenomedullin gene in adipocytes. Biochem Biophys Res Commun 2009,379:98-103.
157 Rosenfield RL:Clinical practice. Hirsutism. N Engl J Med 2005, 353:2578-2588.
158 Du X, Rosenfield RL, Qin K:KLF15 Is a transcriptional regulator of the human 17beta-hydroxysteroid dehydrogenase type 5 gene. A potential link between regulation of testosterone production and fat stores in women. J Clin Endocrinol Metab 2009,94:2594-2601.
159 Gaston K, Jayaraman PS:Transcriptional repression in eukaryotes: repressors and repression mechanisms. Cell Mol Life Sci 2003,60:721-741.
160 Ogata K, Sato K, Tahirov TH:Eukaryotic transcriptional regulatory complexes:cooperativity from near and afar. Curr Opin Struct Biol 2003, 13:40-48.
1 Hey PJ, Twells RC, Phillips MS, Yusuke N, Brown SD, Kawaguchi Y, Cox R, Guochun X, Dugan V, Hammond H, Metzker ML, Todd JA, Hess JF:Cloning of a novel member of the low-density lipoprotein receptor family. Gene 1998,216:103-111.
2 Wehrli M, Dougan ST, Caldwell K, O'Keefe L, Schwartz S, Vaizel-Ohayon D, Schejter E, Tomlinson A, DiNardo S:arrow encodes an LDL-receptor-related protein essential for Wingless signalling. Nature 2000, 407:527-530.
3 Tamai K, Semenov M, Kato Y, Spokony R, Liu C, Katsuyama Y, Hess F, Saint-Jeannet JP, He X:LDL-receptor-related proteins in Wnt signal transduction. Nature 2000,407:530-535.
4 Gong Y, Slee RB, Fukai N, Rawadi G, Roman-Roman S, Reginato AM, Wang H, Cundy T, Glorieux FH, Lev D, Zacharin M, Oexle K, Marcelino J, Suwairi W, Heeger S, Sabatakos G, Apte S, Adkins WN, Allgrove J, Arslan-Kirchner M, Batch JA, Beighton P, Black GC, Boles RG, Boon LM, Borrone C, Brunner HG, Carle GF, Dallapiccola B, De Paepe A, Floege B, Halfliide ML, Hall B, Hennekam RC, Hirose T, Jans A, Juppner H, Kim CA, Keppler-Noreuil K, Kohlschuetter A, LaCombe D, Lambert M, Lemyre E, Letteboer T, Peltonen L, Ramesar RS, Romanengo M, Somer H, Steichen-Gersdorf E, Steinmann B, Sullivan B, Superti-Furga A, Swoboda W, van den Boogaard MJ, Van Hul W, Vikkula M, Votruba M, Zabel B, Garcia T, Baron R, Olsen BR, Warman ML: LDL receptor-related protein 5 (LRP5) affects bone accrual and eye development. Cell 2001,107:513-523.
5 Kato M, Patel MS, Levasseur R, Lobov I, Chang BH, Glass DA,2nd, Hartmann C, Li L, Hwang TH, Brayton CF, Lang RA, Karsenty G, Chan L: Cbfal-independent decrease in osteoblast proliferation, osteopenia, and persistent embryonic eye vascularization in mice deficient in Lrp5, a Wnt coreceptor. J Cell Biol 2002,157:303-314.
6 Boyden LM, Mao J, Belsky J, Mitzner L, Farhi A, Mitnick MA, Wu D, Insogna K, Lifton RP:High bone density due to a mutation in LDL-receptor-related protein 5. N Engl JMed 2002,346:1513-1521.
7 Little RD, Carulli JP, Del Mastro RG, Dupuis J, Osborne M, Folz C, Manning SP, Swain PM, Zhao SC, Eustace B, Lappe MM, Spitzer L, Zweier S, Braunschweiger K, Benchekroun Y, Hu X, Adair R, Chee L, FitzGerald MG, Tulig C, Caruso A, Tzellas N, Bawa A, Franklin B, McGuire S, Nogues X, Gong G, Allen KM, Anisowicz A, Morales AJ, Lomedico PT, Recker SM, Van Eerdewegh P, Recker RR, Johnson ML:A mutation in the LDL receptor-related protein 5 gene results in the autosomal dominant high-bone-mass trait. Am JHum Genet 2002,70:11-19.
8 Van Wesenbeeck L, Cleiren E, Gram J, Beals RK, Benichou O, Scopelliti D, Key L, Renton T, Bartels C, Gong Y, Warman ML, De Vernejoul MC, Bollerslev J, Van Hul W:Six novel missense mutations in the LDL receptor-related protein 5 (LRP5) gene in different conditions with an increased bone density. Am JHum Genet 2003,72:763-771.
9 Babij P, Zhao W, Small C, Kharode Y, Yaworsky PJ, Bouxsein ML, Reddy PS, Bodine PV, Robinson JA, Bhat B, Marzolf J, Moran RA, Bex F:High bone mass in mice expressing a mutant LRP5 gene. J Bone Miner Res 2003, 18:960-974.
10 Urano T, Shiraki M, Ezura Y, Fujita M, Sekine E, Hoshino S, Hosoi T, Orimo H, Emi M, Ouchi Y, Inoue S:Association of a single-nucleotide polymorphism in low-density lipoprotein receptor-related protein 5 gene with bone mineral density. J Bone Miner Metab 2004,22:341-345.
11 Ferrari SL, Deutsch S, Antonarakis SE:Pathogenic mutations and polymorphisms in the lipoprotein receptor-related protein 5 reveal a new biological pathway for the control of bone mass. Curr Opin Lipidol 2005, 16:207-214.
12 Koller DL, Ichikawa S, Johnson ML, Lai D, Xuei X, Edenberg HJ, Conneally PM, Hui SL, Johnston CC, Peacock M, Foroud T, Econs MJ:Contribution of the LRP5 gene to normal variation in peak BMD in women. J Bone Miner Res 2005,20:75-80.
13 Kiel DP, Ferrari SL, Cupples LA, Karasik D, Manen D, Imamovic A, Herbert AG, Dupuis J:Genetic variation at the low-density lipoprotein receptor-related protein 5 (LRP5) locus modulates Wnt signaling and the relationship of physical activity with bone mineral density in men. Bone 2007,40:587-596.
14 Jiao X, Ventruto V, Trese MT, Shastry BS, Hejtmancik JF:Autosomal recessive familial exudative vitreoretinopathy is associated with mutations in LRP5. Am JHum Genet 2004,75:878-884.
15 Qin M, Hayashi H, Oshima K, Tahira T, Hayashi K, Kondo H:Complexity of the genotype-phenotype correlation in familial exudative vitreoretinopathy with mutations in the LRP5 and/or FZD4 genes. Hum Mutat 2005, 26:104-112.
16 Toomes C, Bottomley HM, Jackson RM, Towns KV, Scott S, Mackey DA, Craig JE, Jiang L, Yang Z, Trembath R, Woodruff G, Gregory-Evans CY, Gregory-Evans K, Parker MJ, Black GC, Downey LM, Zhang K, Inglehearn CF: Mutations in LRP5 or FZD4 underlie the common familial exudative vitreoretinopathy locus on chromosome 11q. Am J Hum Genet 2004, 74:721-730.
17 Xu Q, Wang Y, Dabdoub A, Smallwood PM, Williams J, Woods C, Kelley MW, Jiang L, Tasman W, Zhang K, Nathans J:Vascular development in the retina and inner ear:control by Norrin and Frizzled-4, a high-affinity ligand-receptor pair. Cell 2004,116:883-895.
18 Fujino T, Asaba H, Kang MJ, Ikeda Y, Sone H, Takada S, Kim DH, Ioka RX, Ono M, Tomoyori H, Okubo M, Murase T, Kamataki A, Yamamoto J, Magoori K, Takahashi S, Miyamoto Y, Oishi H, Nose M, Okazaki M, Usui S, Imaizumi K, Yanagisawa M, Sakai J, Yamamoto TT:Low-density lipoprotein receptor-related protein 5 (LRP5) is essential for normal cholesterol metabolism and glucose-induced insulin secretion. Proc Natl Acad Sci U S A 2003,100:229-234.
19 Magoori K, Kang MJ, Ito MR, Kakuuchi H, Ioka RX, Kamataki A, Kim DH, Asaba H, Iwasaki S, Takei YA, Sasaki M, Usui S, Okazaki M, Takahashi S, Ono M, Nose M, Sakai J, Fujino T, Yamamoto TT:Severe hypercholesterolemia, impaired fat tolerance, and advanced atherosclerosis in mice lacking both low density lipoprotein receptor-related protein 5 and apolipoprotein E. JBiol Chem 2003,278:11331-11336.
20 Hagen G, Muller S, Beato M, Suske G:Spl-mediated transcriptional activation is repressed by Sp3. Embo J1994,13:3843-3851.
21 Xia Y, Jiang B, Zou Y, Gao G, Shang L, Chen B, Liu Q, Gong Y:Spl and CREB regulate basal transcription of the human SNF2L gene. Biochem Biophys Res Commun 2008,368:438-444.
22 Bieker JJ:Kruppel-like factors:three fingers in many pies. JBiol Chem 2001, 276:34355-34358.
23 Kaczynski J, Cook T, Urrutia R:Spl-and Kruppel-like transcription factors. Genome Biol 2003,4:206.
24 Cook T, Gebelein B, Belal M, Mesa K, Urrutia R:Three conserved transcriptional repressor domains are a defining feature of the TIEG subfamily of Spl-like zinc finger proteins. J Biol Chem 1999, 274:29500-29504.
25 Gray S, Feinberg MW, Hull S, Kuo CT, Watanabe M, Sen-Banerjee S, DePina A, Haspel R, Jain MK:The Kruppel-like factor KLF15 regulates the insulin-sensitive glucose transporter GLUT4. J Biol Chem 2002, 277:34322-34328.
26 Otteson DC, Liu Y, Lai H, Wang C, Gray S, Jain MK, Zack DJ:Kruppel-like factor 15, a zinc-finger transcriptional regulator, represses the rhodopsin and interphotoreceptor retinoid-binding protein promoters. Invest Ophthalmol Vis Sci 2004,45:2522-2530.
27 Uchida S, Tanaka Y, Ito H, Saitoh-Ohara F, Inazawa J, Yokoyama KK, Sasaki S, Marumo F:Transcriptional regulation of the CLC-K1 promoter by myc-associated zinc finger protein and kidney-enriched Kruppel-like factor, a novel zinc finger repressor. Mol Cell Biol 2000,20:7319-7331.
28 Yamamoto J, Ikeda Y, Iguchi H, Fujino T, Tanaka T, Asaba H, Iwasaki S, Ioka RX, Kaneko IW, Magoori K, Takahashi S, Mori T, Sakaue H, Kodama T, Yanagisawa M, Yamamoto TT, Ito S, Sakai J:A Kruppel-like factor KLF15 contributes fasting-induced transcriptional activation of mitochondrial acetyl-CoA synthetase gene AceCS2. J Biol Chem 2004,279:16954-16962.
29 Suske G:The Sp-family of transcription factors. Gene 1999,238:291-300.
30 Philipsen S, Suske G:A tale of three fingers:the family of mammalian Sp/XKLF transcription factors. Nucleic Acids Res 1999,27:2991-3000.
1 Bieker JJ:Kruppel-like factors:three fingers in many pies. J Biol Chem 2001, 276:34355-34358.
2 Black AR, Black JD, Azizkhan-Clifford J:Spl and kruppel-like factor family of transcription factors in cell growth regulation and cancer. J Cell Physiol 2001,188:143-160.
3 Kaczynski J, Cook T, Urrutia R:Spl-and Kruppel-like transcription factors. Genome Biol 2003,4:206.
4 Uchida S, Tanaka Y, Ito H, Saitoh-Ohara F, Inazawa J, Yokoyama KK, Sasaki S, Marumo F: Transcriptional regulation of the CLC-K1 promoter by myc-associated zinc finger protein and kidney-enriched Kruppel-like factor, a novel zinc finger repressor. Mol Cell Biol 2000, 20:7319-7331.
5 Otteson DC, Liu Y, Lai H, Wang C, Gray S, Jain MK, Zack DJ:Kruppel-like factor 15, a zinc-finger transcriptional regulator, represses the rhodopsin and interphotoreceptor retinoid-binding protein promoters. Invest Ophthalmol Vis Sci 2004,45:2522-2530.
6 Gray S, Feinberg MW, Hull S, Kuo CT, Watanabe M, Sen-Banerjee S, DePina A, Haspel R, Jain MK:The Kruppel-like factor KLF15 regulates the insulin-sensitive glucose transporter GLUT4. JBiol Chem 2002,277:34322-34328.
7 Yamamoto J, Ikeda Y, Iguchi H, Fujino T, Tanaka T, Asaba H, Iwasaki S, Ioka RX, Kaneko IW, Magoori K, Takahashi S, Mori T, Sakaue H, Kodama T, Yanagisawa M, Yamamoto TT, Ito S, Sakai J:A Kruppel-like factor KLF15 contributes fasting-induced transcriptional activation of mitochondrial acetyl-CoA synthetase gene AceCS2. J Biol Chem 2004, 279:16954-16962.
8 Mori T, Sakaue H, Iguchi H, Gomi H, Okada Y, Takashima Y, Nakamura K, Nakamura T, Yamauchi T, Kubota N, Kadowaki T, Matsuki Y, Ogawa W, Hiramatsu R, Kasuga M:Role of Kruppel-like factor 15 (KLF15) in transcriptional regulation of adipogenesis. J Biol Chem 2005,280:12867-12875.
9 Fisch S, Gray S, Heymans S, Haldar SM, Wang B, Pfister O, Cui L, Kumar A, Lin Z, Sen-Banerjee S, Das H, Petersen CA, Mende U, Burleigh BA, Zhu Y, Pinto YM, Liao R, Jain MK:Kruppel-like factor 15 is a regulator of cardiomyocyte hypertrophy. Proc Natl Acad Sci USA 2007,104:7074-7079.
10 Gray S, Wang B, Orihuela Y, Hong EG, Fisch S, Haldar S, Cline GW, Kim JK, Peroni OD, Kahn BB, Jain MK:Regulation of gluconeogenesis by Kruppel-like factor 15. Cell Metab 2007, 5:305-312.
11 Teshigawara K, Ogawa W, Mori T, Matsuki Y, Watanabe E, Hiramatsu R, Inoue H, Miyake K, Sakaue H, Kasuga M:Role of Kruppel-like factor 15 in PEPCK gene expression in the liver. Biochem Biophys Res Commun 2005,327:920-926.
12 Xia Y, Jiang B, Zou Y, Gao G, Shang L, Chen B, Liu Q, Gong Y:Spl and CREB regulate basal transcription of the human SNF2L gene. Biochem Biophys Res Commun 2008, 368:438-444.
13 Suske G:The Sp-family of transcription factors. Gene 1999,238:291-300.
14 Philipsen S, Suske G:A tale of three fingers:the family of mammalian Sp/XKLF transcription factors. Nucleic Acids Res 1999,27:2991-3000.
15 Gonzalez GA, Montminy MR:Cyclic AMP stimulates somatostatin gene transcription by phosphorylation of CREB at serine 133. Cell 1989,59:675-680.
16 Viollet B, Lefrancois-Martinez AM, Henrion A, Kahn A, Raymondjean M, Martinez A: Immunochemical characterization and transacting properties of upstream stimulatory factor isoforms. JBiol Chem 1996,271:1405-1415.
17 Gregor PD, Sawadogo M, Roeder RG:The adenovirus major late transcription factor USF is a member of the helix-loop-helix group of regulatory proteins and binds to DNA as a dimer. Genes Dev 1990,4:1730-1740.
18 Sawadogo M, Van Dyke MW, Gregor PD, Roeder RG:Multiple forms of the human gene-specific transcription factor USF. Ⅰ. Complete purification and identification of USF from HeLa cell nuclei. JBiol Chem 1988,263:11985-11993.
19 Sawadogo M:Multiple forms of the human gene-specific transcription factor USF. Ⅱ. DNA binding properties and transcriptional activity of the purified HeLa USF. JBiol Chem 1988, 263:11994-12001.
20 Sirito M, Walker S, Lin Q, Kozlowski MT, Klein WH, Sawadogo M:Members of the USF family of helix-loop-helix proteins bind DNA as homo-as well as heterodimers. Gene Expr 1992,2:231-240.
21 Sirito M, Lin Q, Maity T, Sawadogo M:Ubiquitous expression of the 43-and 44-kDa forms of transcription factor USF in mammalian cells. Nucleic Acids Res 1994,22:427-433.
22 Henrion AA, Martinez A, Mattei MG, Kahn A, Raymondjean M:Structure, sequence, and chromosomal location of the gene for USF2 transcription factors in mouse. Genomics 1995, 25:36-43.
23 Li N, Seetharam B:A 69-base pair fragment derived from human transcobalamin Ⅱ promoter is sufficient for high bidirectional activity in the absence of a TATA box and an initiator element in transfected cells. Role of an E box in transcriptional activity. J Biol Chem 1998,273:28170-28177.
24 Ge Y, Konrad MA, Matherly LH, Taub JW:Transcriptional regulation of the human cystathionine beta-synthase-1b basal promoter:synergistic transactivation by transcription factors NF-Y and Spl/Sp3. Biochem J 2001,357:97-105.
25 Ge Y, Jensen TL, Matherly LH, Taub JW:Physical and functional interactions between USF and Spl proteins regulate human deoxycytidine kinase promoter activity. J Biol Chem 2003, 278:49901-49910.
26 Quinn PG:Distinct activation domains within cAMP response element-binding protein (CREB) mediate basal and cAMP-stimulated transcription. J Biol Chem 1993, 268:16999-17009.
27 Mayr B, Montminy M:Transcriptional regulation by the phosphorylation-dependent factor CREB. Nat Rev Mol Cell Biol 2001,2:599-609.