家蚕bHLH转录因子家族成员鉴定及其基因的电子克隆
|
摘要
bHLH(basic helix-loop-helix,碱性螺旋-环-螺旋)转录因子构成了真核生物蛋白质中的一个大家族,其成员在生物的生长发育调控过程中起着极为重要的作用。bHLH基序约含60个氨基酸,由一个能与DNA结合的碱性区域(basic region)和α螺旋1-环-α螺旋2(Helix 1-Loop-Helix 2)组成,其中环的长度在不同bHLH蛋白中会有差异。自从1989年第一个bHLH蛋白的结构被解析以来,迄今为止已经有近1000条bHLH序列在不同生物中得到鉴定。动物bHLH因其调控基因表达的功能不同而被分成45个家族;此外,根据它们所作用DNA元件和自身结构特点又被分成6个组。A组包含22个家族,主要调控神经细胞生成、肌细胞生成和中胚层形成;B组包含12个家族,主要调控细胞增殖与分化、固醇代谢与脂肪细胞形成以及葡萄糖响应基因的表达;C组包含7个家族,主要负责调控中线与气管发育、昼夜节律、激活环境毒素响应基因的转录;D组只有1个家族,它与A组bHLH蛋白形成无活性的异源二聚体;E组有2个家族,调控胚胎分节、体节形成与器官发生等;F组也只有1个家族,调控头部发育、嗅觉神经元生成等。
迄今为止,生物基因组中的bHLH家族成员数得到鉴定的动物共有15种,其中,人类118个、小鼠102个、河豚84个、文昌鱼78个、星形海葵68个、帽贝63个、Capitella sp.Ⅰ64个、果蝇59个、水蚤57个、紫海胆50个、红粉甲虫50个、玻璃海鞘46个、线虫39个、水螅33个、海绵16个。
家蚕是重要的鳞翅目模式昆虫,家蚕基因组测序工作在2003年10月即已完成,而对于其中有多少个bHLH家族成员还未有报道。本研究采用生物信息学方法开展“家蚕bHLH转录因子家族成员的鉴定及其基因的电子克隆”方面的探索,目的在于鉴定出家蚕中bHLH转录因子家族成员的数目,并初步弄清家蚕中编码bHLH转录因子的基因结构。主要结果如下:
1、家蚕基因组中存在52个bHLH转录因子编码区域,这一结果与其它昆虫中的bHLH数目相近。其中,在12个家蚕bHLH基序的编码区域中有内含子,1个家蚕bHLH基序在基因组中存在两个为其编码的区域,分别位于Ctg038409和Ctg063456上。
2、家蚕52个bHLH转录因子成员的分组及其家族归属情况为:A组21个,分别为BmASCa1、BmASCa2、BmASCa3、BmASCa4、BmMyoD、BmE12/E47、BmNgn、BmAtonal、BmMist、BmBeta3、BmNet、BmDeliah、BmMesp、BmTwist、BmParaxis、BmMyoRa、BmHand、BmPTFa、BmPTFb、BmSCL和BmNSCL;B组10个,分别为BmSRC、BmMyc、BmMnt、BmMax、BmUSF、BmMITF、BmSREBP、BmAP4、BmMLX和BmTF4;C组12个,分别为BmClock1、BmClock2、BmClock3、BmARNT、BmBmal1、BmBmal2、BmAHR1、BmAHR2、BmAHR3、BmSim、BmTrh和BmHIF;D组1个,即BmEmc;E组7个,分别为BmHey1、BmHey2、BmH/E(spl)1、BmH/E(spl)2、BmH/E(spl)3、BmH/E(spl)4和BmH/E(spl)5;F组1个,即BmCOE。在家蚕基因组中没有发现编码ASCb、NeuroD、Oligo、MyoRb、Figα和Mad家族bHLH蛋白的区域。
3、应用电子克隆方法绘制出了11种家蚕bHLH的基因结构,分别是:BmASCa4、BmAtonal、BmBeta3、BmMesp、BmTwist、BmParaxis、BmMyoRa、BmMyc、BmUSF、BmEmc和BmH/E(spl)4;另外,对5种家蚕bHLH蛋白(BmMLX、BmTF4、BmClock1、BmARNT和BmHIF)的编码区域有了一定的了解。
4、预测出了5种家蚕bHLH蛋白的功能,具体为:BmASCa4由l'sc基因编码,具有促进神经前体形成的功能;BmAtonal由αto基因编码,具有调控弦音器与光感受器形成的功能:BmTwist的作用是控制中胚层谱系分化以及抑制MyoD转录因子的功能;BmMyoRa的功能是抑制肌肉细胞的生成;BmEmc与其它bHLH蛋白形成无DNA结合能力的异型二聚体来对生长发育过程实施负调控。
5、本研究还还对人类、大鼠、小鼠、红粉甲虫、果蝇、埃及伊蚊、非洲疟蚊、蜜蜂、鸡、蟾蜍、斑马鱼和海胆的emc基因做了电子克隆。从它们的结构上看,随着生物进化程度的提高,emc基因的外显子和内含子长度似乎有逐步缩短的趋势,倾向于支持内含子早现说。
本研究所获得的结果为今后开展家蚕生长发育调控机理方面的研究积累了基础资料,也为进一步开展这些基因的表达谱分析、不同物种间bHLH基因结构与功能的比较等方面的探索打下了良好基础。
Basic helix-loop-helix transcription factors form a super family of eukaryotic proteins.Its members play crucial roles in the regulation of organismal growth and development.The bHLH motif is composed of approximately 60 amino acids.It has one basic region,which is capable of binding DNA,and a HLH(Helix 1-Loop-Helix 2) structure,in which the loop region varies in different bHLH proteins.Since the discovery of the first bHLH protein in 1989,nearly 1000 bHLH sequences have been identified in various organisms.Animal bHLHs have been classified into 45 families according to their varied roles in regulating gene expression.Besides,they are divided into 6 groups based on their target DNA elements and their own structural characteristics.Group A has 22 families,They mainly regulate neurogenesis, myogenesis and mesoderm formation.Group B has 12 families.They mainly regulate cell proliferation and differentiation,sterol metabolism and adipocyte formation,and glucose-responsive gene expression.Group C has 7 families.They are responsible for the regulation of midline and tracheal development,circadian rhythms,and for the activation of gene transcription in response to environmental toxins.Group D has only 1 family.It forms inactive heterodimers with group A bHLH proteins.Group E has 2 families,which regulate embryonic segmentation,somitogenesis and organogenesis etc. Group F also has 1 family.It regulates head development and formation of olfactory sensory neurons etc.
So far,the total number of animals of which bHLH family members have been identified is 15.The members identified in each species are 118 in human,102 in mouse, 84 in puffer fish,78 in lancelet,68 in sea anemone,63 in Lottia gigantea,64 in Capitella sp.I,59 in fruit fly,57 in Daphnia pulex,50 in sea urchin,50 in red flour beetle,46 in sea squirt,39 in nematode,33 in Hydra magnipapillata and 16 in sponge.
Silkworm(Bombyx mori)is an important model insect of Lepidoptera.Silkworm genome sequencing project has been finished in October 2003.However,there has been no report on how many bHLH family members existing in the genome.This study employed bioinformatic methods to conduct studies on "Identification of bHLH transcription factor family members in Bombyx mori and in silico cloning of their genes".Its objectives includes to find out the number of bHLH transcription factor family members in silkworm and to explore gene structures that code for the bHLH transcription factors.The major results obtained are as follows:
1.The silkworm genome has regions that code for 52 bHLH transcription factors. This figure is comparable with those in other insects.Twelve of the silkworm bHLH motifs have introns.One of them has two coding regions,locating on Ctg038409 and Ctg063456 respectively.
2.All 52 identified silkworm bHLH transcription factors have been assigned into their corresponding groups and families.It was found that group A has 21 silkworm bHLH members.They are BmASCal,BmASCa2,BmASCa3,BmASCa4,BmMyoD, BmE12/E47,BmNgn,BmAtonal,BmMist,BmBeta3,BmNet,BmDeliah,BmMesp, BmTwist,BmParaxis,BmMyoRa,BmHand,BmPTFa,BmPTFb,BmSCL and BmNSCL.Group B has 10 members.They are BmSRC,BmMyc,BmMnt,BmMax, BmUSF,BmMITF,BmSREBP,BmAP4,BmMLX and BmTF4.Group C has 12 members.They are BmClock1,BmClock2,BmClock3,BmARNT,BmBma11, BmBma12,BmAHR1,BmAHR2,BmAHR3,BmSim,BmTrh and BmHIF.Group D has one member,BmEmc.Group E has 7 members.They are Hey1,BmHey2, BmH/E(spl)1,BmH/E(spl)2,BmH/E(spl)3,BmH/E(spl)4 and BmH/E(spl)5.Group F has one member,BmCOE.Coding regions for ASCb,NeuroD,Oligo,MyoRb,Figαand Mad families were not found in silkworm genome.
3.Structural information of 11 silkworm bHLH genes was obtained through in silico cloning.They are BmASCa4,BmAtonal,BmBeta3,BmMesp,BmTwist, BmParaxis,BmMyoRa,BmMyc,BmUSF,BmEmc and BmH/E(spl)4.Partial structural information of 5 silkworm bHLH genes was also obtained.They are BmMLX,BmTF4, BmClock1,BmARNT and BmHIF.
4.Functions of 5 BmbHLH proteins have been deduced,among which BmASCa4 is encoded by l'sc gene and promotes formation of neural precursers;BmAtonal is encoded by ato gene and controls the formation of chordotonal organs and photoreceptors;BmTwist plays roles in controlling differentiation of mesodermal lineage and inhibiting functions of transcription factor MyoD;BmMyoRa inhibits the formation of muscle cells;and BmEmc exerts negative control through forming heterodimers that lack DNA-binding ability with other bHLH proteins.
5.Emc gene structures have also been explored in human,rat,mouse,red flour beetle,fruit fly,Aedes aegypti,Anopheles gambie str.PEST,honeybee,chicken, Xenopus,zebrafish and sea urchin.Based on their structures,it seems that,as the evolutionary level of the organisms heightens,exon and intron lengths of the Emc genes shorten gradually,tending to support the introns-early theory.
The achievements of this study accrued fundamental knowledge for future studies on regulating mechanisms of silkworm growth and development.They can also facilitate further studies on expression patterns of the bHLH genes and on comparison of bHLH gene structures and functions between different species.
迄今为止,生物基因组中的bHLH家族成员数得到鉴定的动物共有15种,其中,人类118个、小鼠102个、河豚84个、文昌鱼78个、星形海葵68个、帽贝63个、Capitella sp.Ⅰ64个、果蝇59个、水蚤57个、紫海胆50个、红粉甲虫50个、玻璃海鞘46个、线虫39个、水螅33个、海绵16个。
家蚕是重要的鳞翅目模式昆虫,家蚕基因组测序工作在2003年10月即已完成,而对于其中有多少个bHLH家族成员还未有报道。本研究采用生物信息学方法开展“家蚕bHLH转录因子家族成员的鉴定及其基因的电子克隆”方面的探索,目的在于鉴定出家蚕中bHLH转录因子家族成员的数目,并初步弄清家蚕中编码bHLH转录因子的基因结构。主要结果如下:
1、家蚕基因组中存在52个bHLH转录因子编码区域,这一结果与其它昆虫中的bHLH数目相近。其中,在12个家蚕bHLH基序的编码区域中有内含子,1个家蚕bHLH基序在基因组中存在两个为其编码的区域,分别位于Ctg038409和Ctg063456上。
2、家蚕52个bHLH转录因子成员的分组及其家族归属情况为:A组21个,分别为BmASCa1、BmASCa2、BmASCa3、BmASCa4、BmMyoD、BmE12/E47、BmNgn、BmAtonal、BmMist、BmBeta3、BmNet、BmDeliah、BmMesp、BmTwist、BmParaxis、BmMyoRa、BmHand、BmPTFa、BmPTFb、BmSCL和BmNSCL;B组10个,分别为BmSRC、BmMyc、BmMnt、BmMax、BmUSF、BmMITF、BmSREBP、BmAP4、BmMLX和BmTF4;C组12个,分别为BmClock1、BmClock2、BmClock3、BmARNT、BmBmal1、BmBmal2、BmAHR1、BmAHR2、BmAHR3、BmSim、BmTrh和BmHIF;D组1个,即BmEmc;E组7个,分别为BmHey1、BmHey2、BmH/E(spl)1、BmH/E(spl)2、BmH/E(spl)3、BmH/E(spl)4和BmH/E(spl)5;F组1个,即BmCOE。在家蚕基因组中没有发现编码ASCb、NeuroD、Oligo、MyoRb、Figα和Mad家族bHLH蛋白的区域。
3、应用电子克隆方法绘制出了11种家蚕bHLH的基因结构,分别是:BmASCa4、BmAtonal、BmBeta3、BmMesp、BmTwist、BmParaxis、BmMyoRa、BmMyc、BmUSF、BmEmc和BmH/E(spl)4;另外,对5种家蚕bHLH蛋白(BmMLX、BmTF4、BmClock1、BmARNT和BmHIF)的编码区域有了一定的了解。
4、预测出了5种家蚕bHLH蛋白的功能,具体为:BmASCa4由l'sc基因编码,具有促进神经前体形成的功能;BmAtonal由αto基因编码,具有调控弦音器与光感受器形成的功能:BmTwist的作用是控制中胚层谱系分化以及抑制MyoD转录因子的功能;BmMyoRa的功能是抑制肌肉细胞的生成;BmEmc与其它bHLH蛋白形成无DNA结合能力的异型二聚体来对生长发育过程实施负调控。
5、本研究还还对人类、大鼠、小鼠、红粉甲虫、果蝇、埃及伊蚊、非洲疟蚊、蜜蜂、鸡、蟾蜍、斑马鱼和海胆的emc基因做了电子克隆。从它们的结构上看,随着生物进化程度的提高,emc基因的外显子和内含子长度似乎有逐步缩短的趋势,倾向于支持内含子早现说。
本研究所获得的结果为今后开展家蚕生长发育调控机理方面的研究积累了基础资料,也为进一步开展这些基因的表达谱分析、不同物种间bHLH基因结构与功能的比较等方面的探索打下了良好基础。
Basic helix-loop-helix transcription factors form a super family of eukaryotic proteins.Its members play crucial roles in the regulation of organismal growth and development.The bHLH motif is composed of approximately 60 amino acids.It has one basic region,which is capable of binding DNA,and a HLH(Helix 1-Loop-Helix 2) structure,in which the loop region varies in different bHLH proteins.Since the discovery of the first bHLH protein in 1989,nearly 1000 bHLH sequences have been identified in various organisms.Animal bHLHs have been classified into 45 families according to their varied roles in regulating gene expression.Besides,they are divided into 6 groups based on their target DNA elements and their own structural characteristics.Group A has 22 families,They mainly regulate neurogenesis, myogenesis and mesoderm formation.Group B has 12 families.They mainly regulate cell proliferation and differentiation,sterol metabolism and adipocyte formation,and glucose-responsive gene expression.Group C has 7 families.They are responsible for the regulation of midline and tracheal development,circadian rhythms,and for the activation of gene transcription in response to environmental toxins.Group D has only 1 family.It forms inactive heterodimers with group A bHLH proteins.Group E has 2 families,which regulate embryonic segmentation,somitogenesis and organogenesis etc. Group F also has 1 family.It regulates head development and formation of olfactory sensory neurons etc.
So far,the total number of animals of which bHLH family members have been identified is 15.The members identified in each species are 118 in human,102 in mouse, 84 in puffer fish,78 in lancelet,68 in sea anemone,63 in Lottia gigantea,64 in Capitella sp.I,59 in fruit fly,57 in Daphnia pulex,50 in sea urchin,50 in red flour beetle,46 in sea squirt,39 in nematode,33 in Hydra magnipapillata and 16 in sponge.
Silkworm(Bombyx mori)is an important model insect of Lepidoptera.Silkworm genome sequencing project has been finished in October 2003.However,there has been no report on how many bHLH family members existing in the genome.This study employed bioinformatic methods to conduct studies on "Identification of bHLH transcription factor family members in Bombyx mori and in silico cloning of their genes".Its objectives includes to find out the number of bHLH transcription factor family members in silkworm and to explore gene structures that code for the bHLH transcription factors.The major results obtained are as follows:
1.The silkworm genome has regions that code for 52 bHLH transcription factors. This figure is comparable with those in other insects.Twelve of the silkworm bHLH motifs have introns.One of them has two coding regions,locating on Ctg038409 and Ctg063456 respectively.
2.All 52 identified silkworm bHLH transcription factors have been assigned into their corresponding groups and families.It was found that group A has 21 silkworm bHLH members.They are BmASCal,BmASCa2,BmASCa3,BmASCa4,BmMyoD, BmE12/E47,BmNgn,BmAtonal,BmMist,BmBeta3,BmNet,BmDeliah,BmMesp, BmTwist,BmParaxis,BmMyoRa,BmHand,BmPTFa,BmPTFb,BmSCL and BmNSCL.Group B has 10 members.They are BmSRC,BmMyc,BmMnt,BmMax, BmUSF,BmMITF,BmSREBP,BmAP4,BmMLX and BmTF4.Group C has 12 members.They are BmClock1,BmClock2,BmClock3,BmARNT,BmBma11, BmBma12,BmAHR1,BmAHR2,BmAHR3,BmSim,BmTrh and BmHIF.Group D has one member,BmEmc.Group E has 7 members.They are Hey1,BmHey2, BmH/E(spl)1,BmH/E(spl)2,BmH/E(spl)3,BmH/E(spl)4 and BmH/E(spl)5.Group F has one member,BmCOE.Coding regions for ASCb,NeuroD,Oligo,MyoRb,Figαand Mad families were not found in silkworm genome.
3.Structural information of 11 silkworm bHLH genes was obtained through in silico cloning.They are BmASCa4,BmAtonal,BmBeta3,BmMesp,BmTwist, BmParaxis,BmMyoRa,BmMyc,BmUSF,BmEmc and BmH/E(spl)4.Partial structural information of 5 silkworm bHLH genes was also obtained.They are BmMLX,BmTF4, BmClock1,BmARNT and BmHIF.
4.Functions of 5 BmbHLH proteins have been deduced,among which BmASCa4 is encoded by l'sc gene and promotes formation of neural precursers;BmAtonal is encoded by ato gene and controls the formation of chordotonal organs and photoreceptors;BmTwist plays roles in controlling differentiation of mesodermal lineage and inhibiting functions of transcription factor MyoD;BmMyoRa inhibits the formation of muscle cells;and BmEmc exerts negative control through forming heterodimers that lack DNA-binding ability with other bHLH proteins.
5.Emc gene structures have also been explored in human,rat,mouse,red flour beetle,fruit fly,Aedes aegypti,Anopheles gambie str.PEST,honeybee,chicken, Xenopus,zebrafish and sea urchin.Based on their structures,it seems that,as the evolutionary level of the organisms heightens,exon and intron lengths of the Emc genes shorten gradually,tending to support the introns-early theory.
The achievements of this study accrued fundamental knowledge for future studies on regulating mechanisms of silkworm growth and development.They can also facilitate further studies on expression patterns of the bHLH genes and on comparison of bHLH gene structures and functions between different species.
引文
1.Weaver R:Molecular Biology.McGraw-Hill 1999:351-353.
2.Ma P,Rould M,Weintraub H,Pabo C:Crystal structure of MyoD bHLH domain-DNA complex:perspectives on DNA recognition and implications for transcriptional activation.Cell 1994,77(3):451-459.
3.Murre C,McCaw PS,Baltimore D:A new DNA binding and dimerizing motif in immunoglobulin enhancer binding,Daughterless,MyoD,and Myc proteins.Cell 1989,56:777-783.
4.Simionato E,Ledent V,Richards G,Thomas-Chollier M,Kerner P,Coornaert D,Degnan BM,Vervoort M:Origin and diversification of the basic helix-loop-helix gene family in metazoans:insights from comparative genomics.BMC Evol Biol 2007,7:33.
5.Massari ME,Murre C:Helix-Loop-Helix Proteins:Regulators of Transcription in Eucaryotic Organisms.Mol Cell Biol 2000,20(2):429-440.
6.Jones DT,Taylor WR,Thornton JM:The rapid generation of mutation data matrices from protein sequences.CABIOS 1992,8:275-282.
7.贺强,王立峰:bHLH蛋白家族的功能.国外医学-生理、病理科学与临床分册2004,24(6):545-547.
8.Atchley WR,Fitch WM:A natural classification of the basic helix-loop-helix class of transcription factors.Proc Natl Acad Sci U S A 1997,94(10):5172-5176.
9.Atchley WR,Terhalle W,Dress A:Positional dependence,cliques,and predictive motifs in the bHLH protein domain.J Mol Evol 1999,48(5):501-516.
10.Moore AW,Barbel S,Jan LY,Jan YN:A genomewide survey of basic helix-loop-helix factors in Drosophila.Proc Natl Acad Sci USA 2000,97(19):10436-10441.
11.Ledent V,Vervoort M:The basic helix-loop-helix protein family:comparative genomics and phyiogenetic analysis.Genome Res 2001,11(5):754-770.
12.Ledent V,Paquet O,Vervoort M:Phylogenetic analysis of the human basic helix-loop-helix proteins.Genome Biol 2002,3(6):RESEARCH0030.
13.Satou Y,Imai KS,Levine M,Kohara Y,Rokhsar D,Satoh N:A genomewide survey of developmentally relevant genes in Ciona intestinalis.I.Genes for bHLH transcription factors.Dev Genes Evol 2003,213(5-6):213-221.
14.Wang Y,Chen KP,Yao Q,Wang WB,Zhu Z:The basic helix-loop-helix transcription factor family in Bombyx mori.Dev Genes Evol 2007,217(10):715-723.
15.Alonso MC,Cabrera CV:The achaete-scutegene complex of Drosophila melanogaster comprises four homologous genes.EMBO J 1988,7:2585-2591.
16.CelegansSequencingConsortium:Genome sequence of the nematode C.elegans:a platform for investigating biology. Science 1998, 282(5396):2012-2018.
17. Weintraub H, Dwarki VJ, Verma I, Davis R, Hollenberg S, Snider L, Lassar A, Tapscott SJ: Muscle-specific transcriptional activation by MyoD. Genes Dev 1991, 5(8): 1377-1386.
18. Sommer L, Ma Q, Anderson DJ: neurogenins, a novel family of atonal-related bHLH transcription factors, are putative mammalian neuronal determination genes that reveal progenitor cell heterogeneity in the developing CNS and PNS. Mol Cell Neurosci 1996, 8(4):221-241.
19. Kho CJ, Huggins GS, Endege WO, Patterson C, Jain MK, Lee ME, Haber E: The polymyositis-scleroderma autoantigen interacts with the helix-loop-helix proteins E12 and E47. J Biol Chem 1997, 272(20): 13426-13431.
20. Jarman AP, Grau Y, Jan LY, Jan YN: atonal is a proneural gene that directs chordotonal organ formation in the Drosophila peripheral nervous system. Cell 1993,73(7): 1307-1321.
21. Lemercier C, To RQ, Swanson BJ, Lyons GE, Konieczny SF: Mist1: a novel basic helix-loop-helix transcription factor exhibits a developmentally regulated expression pattern. Dev Biol 1997,182(1): 101-113.
22. Peyton M, Stellrecht CM, Naya FJ, Huang HP, Samora PJ, Tsai MJ: BETA3, a novel helix-loop-helix protein, can act as a negative regulator of BETA2 and MyoD-responsive genes. Mol Cell Biol 1996, 16(2):626-633.
23. Zhou Q, Wang S, Anderson DJ: Identification of a novel family of oligodendrocyte lineage-specific basic helix-loop-helix transcription factors. Neuron 2000, 25(2):331-343.
24. Brentrup D, Lerch H, Jackie H, Noll M: Regulation of Drosophila wing vein patterning: net encodes a bHLH protein repressing rhomboid and is repressed by rhomboid-dependent Egfr signalling. Development 2000, 127(21 ):4729-4741.
25. Armand P, Knapp AC, Hirsch AJ, Wieschaus EF, Cole MD: A novel basic helix-loop-helix protein is expressed in muscle attachment sites of the Drosophila epidermis. Mol Cell Biol 1994, 14(6):4145-4154.
26. Saga Y, Hata N, Kobayashi S, Magnuson T, Seldin MF, Taketo MM: MesP1: a novel basic helix-loop-helix protein expressed in the nascent mesodermal cells during mouse gastrulation. Development 1996, 122(9):2769-2778.
27. Tapanes-Castillo A, Baylies MK: Notch signaling patterns Drosophila mesodermal segments by regulating the bHLH transcription factor twist. Development 2004, 131(10):2359-2372.
28. Burgess R, Cserjesi P, Ligon KL, Olson EN: Paraxis: a basic helix-loop-helix protein expressed in paraxial mesoderm and developing somites. Dev Biol 1995, 168(2):296-306.
29. Lu J, Webb R, Richardson JA, Olson EN: MyoR: a muscle-restricted basic helix-loop-helix transcription factor that antagonizes the actions of MyoD. Proc Natl Acad Sci U S A 1999, 96(2):552-557.
30. Yokota Y, Mori S, Narumi O, Kitajima K: In vivo function of a differentiation inhibitor, Id2. IUBMB Life 2001, 51(4):207-214.
31. Thomas T, Yamagishi H, Overbeek PA, Olson EN, Srivastava D: The bHLH factors, dHAND and eHAND, specify pulmonary and systemic cardiac ventricles independent of left-right sidedness. Dev Biol 1998,196(2):228-236.
32. Knofler M, Krapp A, Hagenbuchle O, Wellauer PK: Constitutive expression of the gene for the cell-specific p48 DNA-binding subunit of pancreas transcription factor 1 in cultured cells is under control of binding sites for transcription factors Sp1 and alphaCbf. J Biol Chem 1996, 271(36):21993-22002.
33. Lecuyer E, Herblot S, Saint-Denis M, Martin R, Begley CG, Porcher C, Orkin SH, Hoang T: The SCL complex regulates c-kit expression in hematopoietic cells through functional interaction with Sp1. Blood 2002,100(7):2430-2440.
34. Chen SL, Dowhan DH, Hosking BM, Muscat GE: The steroid receptor coactivator, GRIP-1, is necessary for MEF-2C-dependent gene expression and skeletal muscle differentiation. Genes Dev 2000, 14(10): 1209-1228.
35. Dean J: Oocyte-specific genes regulate follicle formation, fertility and early mouse development. J Reprod Immunol 2002, 53( 1 -2): 171 -180.
36. Kaddurah-Daouk R, Greene JM, Baldwin ASJ, Kingston RE: Activation and repression of mammalian gene expression by the c-myc protein. Genes Dev 1987, 1(4):347-357.
37. Ayer D, Kretzner L, Eisenman R: Mad: a heterodimeric partner for Max that antagonizes Myc transcriptional activity. Cell 1993, 72(2):211-222.
38. Hurlin P, Queva C, Eisenman R: Mnt, a novel Max-interacting.protein is coexpressed with Myc in prohferatlng cells and mediates repression at Myc binding sites. Genes & Development 1997, 11(1):44-58.
39. Blackwood EM, Eisenman RN: Max: a helix-loop-helix zipper protein that forms a sequence-specific DNA-binding complex with Myc. Science 1991, 251(4998): 1211-1217.
40. Reisman D, Rotter V: The helix-loop-helix containing transcription factor USF binds to and transactivates the promoter of the p53 tumor suppressor gene. Nucleic Acids Res 1993,21(2):345-350.
41. Nobukuni Y, Watanabe A, Takeda K, Skarka H, Tachibana M: Analyses of loss-of-function mutations of the M1TF gene suggest that haploinsufficiency is a cause of Waardenburg syndrome type 2A. Am J Hum Genet 1996,59(1):76-83.
42. Yokoyama C, Wang X, Briggs MR, Admon A, Wu J, Hua X, Goldstein JL, Brown MS: SREBP-1, a basic-helix-loop-helix-leucine zipper protein that controls transcription of the low density lipoprotein receptor gene. Cell 1993, 75(1): 187-197.
43. Hua X, Yokoyama C, Wu J, Briggs MR, Brown MS, Goldstein JL, Wang X: SREBP-2, a second basic-helix-loop-helix-lcucine zipper protein that stimulates transcription by binding to a sterol regulatory element. Proc Natl Acad Sci U S A 1993, 90(24): 11603-11607.
44. Hu YF, Lüscher B, Admon A, Mermod N, Tjian R: Transcription factor AP-4 contains multiple dimerization domains that regulate dimer specificity. Genes Dev 1990, 4(10):1741-1752.
45. Stoeckman AK, Ma L, Towle HC: Mlx is the functional heteromeric partner of the carbohydrate response element-binding protein in glucose regulation of lipogenic enzyme genes. J Biol Chem 2004, 279(15): 15662-15669.
46. Bjerknes M, Cheng H: TCFL4: a gene at 17q21.1 encoding a putative basic helix-loop-helix leucine-zipper transcription factor. Gene 1996,181(1-2):7-11.
47. King DP, Zhao Y, Sangoram AM, Wilsbacher LD, Tanaka M, Antoch MP, Steeves TD, Vitaterna MH, Kornhauser JM, Lowrey PL et al. Positional cloning of the mouse circadian clock gene. Cell 1997, 89(4):641-653.
48. Katzenberg D, Young T, Lin L, Finn L, Mignot E: A human period gene (HPER1) polymorphism is not associated with diurnal preference in normal adults. Psychiatr Genet 1999, 9(2):107-109.
49. Hankinson O: The aryl hydrocarbon receptor complex. Annu Rev Pharmacol Toxicol 1995,35:307-340.
50. Muralidhar MG, Callahan CA, Thomas JB: Single-minded regulation of genes in the embryonic midline of the Drosophila central nervous system. Mech Dev 1993, 41(2-3): 129-138.
51. Wilk R, Weizman I, Shilo BZ: trachealess encodes a bHLH-PAS protein that is an inducer of tracheal cell fates in Drosophila. Genes Dev 1996,10(1):93-102.
52. Liu CJ, Ding B, Wang H, Lengyel P: The MyoD-inducible p204 protein overcomes the inhibition of myoblast differentiation by Id proteins. Mol Cell Biol 2002, 22(9):2893-2905.
53. Ellis HM: Embryonic expression and function of the Drosophiia helix-loop-helix gene, extramacrochaetae. Mech Dev 1994, 47(1):65-72.
54. Leimeister C, Externbrink A, Klamt B, Gessler M: Hey genes: a novel subfamily of hairy-and Enhancer of split related genes specifically expressed during mouse embryogenesis. Mech Dev 1999, 85(1-2): 173-177.
55. Wainwright SM, Ish-Horowicz D: Point mutations in the Drosophila hairy gene demonstrate in vivo requirements for basic, helix-loop-helix, and WRPW domains. Mol Cell Biol 1992, 12(6):2475-2483.
56. Maier D, Marte BM, Schafer W, Yu Y, Preiss A: Drosophila evolution challenges postulated redundancy in the E(spl) gene complex. Proc Natl Acad Sci U S A 1993, 90(12):5464-5468.
57. Crozatier M, Valle D, Dubois L, Ibnsouda S, Vincent A: Collier, a novel regulator of Drosophila head development, is expressed in a single mitotic domain. Curr Biol 1996, 6(6):707-718.
58. Kudrycki K, Stein-Izsak C, Behn C, Grillo M, Akeson R, Margolis FL: Olf-1-binding site: characterization of an olfactory neuron-specific promoter motif. Mol Cell Biol 1993, 13(5):3002-3014.
59. Li X, Duan X, Jiang H, Sun Y, Tang Y, Yuan Z, Guo J, Liang W, Chen L, Yin J et al: Genome-wide analysis of basic/helix-loop-helix transcription factor family in rice and Arabidopsis. Plant Physiol 2006,141(4): 1167-1184.
60. Toledo-Ortiz G, Huq E, Quail PH: The Arabidopsis basic/helix-loop-helix transcription factor family. Plant Cell 2003,15(8): 1749-1770.
61. Buck MJ, Atchley WR: Phylogenetic analysis of plant basic helix-loop-helix proteins. J Mol Evol 2003, 56(6):742-750.
62. Heim MA, Jakoby M, Werber M, Martin C, Weisshaar B, Bailey PC: The basic helix-loop-helix transcription factor family in plants: a genome-wide study of protein structure and functional diversity. Mol Biol Evol 2003, 20(5):735-747.
63. Altschul SF, Madden TL, Sch(a|¨)ffer AA, Zhang J, Zhang Z, Miller W, Lipman DJ: Gapped BLAST and PSI-BLAST: a new generation of protein database search programs. Nucleic Acids Res 1997, 25:3389-3402.
64. Seo S, Kroll KL: Geminin's double life: chromatin connections that regulate transcription at the transition from proliferation to differentiation. Cell Cycle 2006, 5(4):374-379.
65. Fischer A, Gessler M: Delta-Notch—and then? Protein interactions and proposed modes of repression by Hes and Hey bHLH factors. Nucleic Acids Res 2007, 35(14):4583-4596.
66. Xia Q, Zhou Z, Lu C, Cheng D, Dai F, Li B, Zhao P, Zha X, Cheng T, Chai C et al: A draft sequence for the genome of the domesticated silkworm (Bombyx mori). Science 2004, 306(5703): 1937-1940.
67. Swofford DL: PAUP* Phylogenetic Analysis Using Parsimony, Version 4. Sinauer Associates, Sunderland, Massachusetts 1998.
68. Kuzoff RK: http://paup.csit.fsu.edu/nfiles.html. 1978.
69. Schmidt HA, K. Strimmer, M. Vingron, and A. von Haeseler TREE-PUZZLE: maximum likelihood phylogenetic analysis using quartets and parallel computing. Bioinformatics 2002, 18:502-504.
70. Tamura K, Dudley J, Nei M, Kumar S: MEGA4: Molecular Evolutionary Genetics Analysis (MEGA) Software Version 4.0. Mol Biol Evol 2007, 24(8): 1596-1599.
71. Nicholas KB, Nicholas-Jr HB, Deerfield-II DW: GeneDoc: Analysis and Visualization of Genetic Variation. Embnet News 1997, 4:14.
72. Fitch W: Distinguishing homologous from analogous proteins. Syst Zool 1970, 19:99-113.
73. Markova EP, Ueda H, Sakamoto K, Oishi K, Shimada T, Takeda M: Cloning of Cyc (Bmal1) homolog in Bombyx mori: structural analysis and tissue specific distributions. Comp Biochem Physiol B Biochem Mol Biol 2003, 134(3):535-542.
74. Matsunami K, Kokubo H, Ohno K, Xu P, Ueno K, Suzuki Y: Embryonic silk gland development in Bombyx: molecular cloning and expression of the Bombyx trachealess gene. Dev Genes Evol 1999, 209:507-514.
75. Zelzer E, Wappner P, Shilo B-Z: The PAS domain confers target gene specificity of Drosophila bHLH/PAS proteins. Genes Dev 1997, 11(16):2079-2089.
76. Lapan S, 王勇: An introduction to molecular biology wich Chinese translation. 化学工业出版社 2008:106.
77. Koonin E: The origin of introns and their role in eukaryogenesis: a compromise solution to the introns-early versus introns-late debate? Biol Direct 2006, 10.1186( 1745-6150): 1 -22.
78. Nguyen H, Yoshihama M, Kenmochi N: Phase distribution of spliceosomal introns: implications for intron origin. BMC Evol Biol 2006, 6:69-78.
79. Cubas P, deCelis J, Campuzano S, Modolell J: Proneural clusters of achaete-scute expression and the generation of sensory organs in the Drosophila imaginal wing disc. Genes Dev 1991, 5(996-1008):996.
80. Skeath J, Carroll S: Regulation of achaete-scute gene expression and sensory organ pattern formation in the Drosophila wing. Genes Dev 1991, 5:984-995.
81. Jan Y, Jan L: Genetic control of cell fate specification in Drosophila peripheral nervous system. Annu Rev Genet 1994, 28:373-393.
82. Wheeler S, Carrico M, Wilson B, Brown S, Skeath J: The expression and function of the achaete-scute genes in Tribolium castaneum reveals conservation and variation in neural pattern formation and cell fate specification. Development 2003,130(18):4373-4381.
83. Takano T: Rate variation of DNA sequence evolution in the Drosophila lineages. Genetics Genetics, 149(2):959-970.
84. Carmena A, Bate M, Jimenez F: Lethal of scute, a proneural gene, participates in the specification of muscle progenitors during Drosophila embryogenesis. Genes Dev 1995, 9(19):2373-2383.
85. Grillenzoni N, de Vaux V, Meuwly J, Vuichard S, Jarman A, Holohan E, Gendre N, Stacker RF: Role of proneural genes in the formation of the larval olfactory organ of Drosophila. Dev Genes Evol 2007, 217(3):209-219.
86. Goulding S, White N, Jarman A: cato encodes a basic helix-loop-helix transcription factor implicated in the correct differentiation of Drosophila sense organs. Dev Biol 2000, 221(1): 120-131.
87. Jarman A, Sun Y, Jan L, Jan Y: Role of the proneural gene, atonal, in formation of Drosophila chordotonal organs and photoreceptors. Development 1995, 121(7):2019-2030.
88. zur Lage PI, Prentice DR, Holohan EE, Jarman AP: The Drosophila proneural gene amos promotes olfactory sensillum formation and suppresses bristle formation. Development 2003,130(19):4683-4693.
89. Kim MH, Gunnersen J, Augustine C, Tan SS: Region-specific expression of the helix-loop-helix gene BETA3 in developing and adult brains. Mech Dev 2002, 114(1-2):125-128.
90. Morimoto M, Kiso M, Sasaki N, Saga Y: Cooperative Mesp activity is required for normal somitogenesis along the anterior-posterior axis. Dev Biol 2006,300(2):687-698.
91. Castanon I, Von Stetina S, Kass J, Baylies MK: Dimerization partners determine the activity of the Twist bHLH protein during Drosophila mesoderm development. Development 2001, 128(16):3145-3159.
92. Spicer D, Rhee J, Cheung W, Lassar A: Inhibition of myogenic bHLH and MEF2 transcription factors by the bHLH protein twist. Science 1996, 272:1476-1480.
93. Hamamori Y, Wu HY, Sartorelli V, Kedes L: he basic domain of myogenic basic helix-loop-helix (bHLH) proteins is the novel target for direct inhibition by another bHLH protein, Twist. Mol Cell Biol 1997,17:6563-6573.
94. Yu L, Sangster N, Perez A, McCormick PJ: The bHLH protein MyoR inhibits the differentiation of early embryonic endoderm. Differentiation 2004, 72(7):341-347.
95. Facchini L, Penn L: The molecular role of Myc in growth and transformation: recent discoveries lead to new insights. FASEB J 1998,12:633-651.
96. Henriksson M, Luscher B: Proteins of the Myc network: essential regulators of cell growth and differentiation. Adv Cancer Res 1996, 68:109-182.
97. Cheng S, Davies K, Yung E, Beltran R, Yu J, Kalpana G: c-MYC interacts with INI1/hSNF5 and requires the SWI/SNF complex for transactivation function. Nat Genet 1999,22:102-105.
98. Cole M: The affairs of daughterless and the promiscuity of developmental regulators. Cell 1989,59:231-234.
99. McMahon S, VanBuskirk H, Dugan K, Copeland T, Cole M: The novel ATM-related protein TRRAP is an essential cofactor for the c-Myc and E2F oncoproteins. Cell 1998, 94:363-374.
100. Jung H, Kim K, Chung Y, Chung H, Min Y, Lee M, Lee M, Kim K, Chung J: USF inhibits cell proliferation through delay in G2/M phase in FRTL-5 cells. Endocr J 2007, 54(2):275-285.
101. Sirito M, Walker S, Lin Q, Kozlowski M, Klein W, Sawadogo M: Members of the USF family of helix-loop-helix proteins bind DNA as homo- as well as heterodimers. Gene Expr 1992, 2(3):231-240.
102. Langlands K, Yin X, Anand G, Prochownik E: Differential interactions of Id proteins with basic-helix-loop-helix transcription factors. J Biol Chem 1997,272:19785-19793.
103. Yan W, Young A, Soares V, Kelley R, Benezra R, Zhuang Y: High incidence of T-cell tumors in E2A-null mice and E2A/Idl double-knockout mice. Mol Cell Biol 1997, 17:7317-7327.
104. Yokota Y, Mansouri A, Mori S, Sugawara S, Adachi S, Nishikawa S, Gruss P: Development of peripheral lymphoid organs and natural killer cells depends on the helix-loop-helix inhibitor Id2. Nature 1999, 397:702-706.
105. Jen Y, Manova K, Benezra R: Expression patterns of Id1, Id2, and Id3 are highly related but distinct from that of Id4 during mouse embryogenesis. Dev Dyn 1996, 207(3):235-252.
106. Yokota Y, Mori S: Role of Id family proteins in growth control. J Cell Physiol 2002, 190(1):21-28.
107. Baonza A, Garcia-Bellido A: Dual role of extramacrochaetae in cell proliferation and cell differentiation during wing morphogenesis in Drosophila. Mech Dev 1999, 80(2): 133-146.
108. Campuzano S: Emc, a negative HLH regulator with multiple functions in Drosophila development. Oncogene 2001, 20(58):8299-8307.
109. Cheng T, Zhao P, Liu C, Xu P, Gao Z, Xia Q, Xiang Z: Structures, regulatory regions, and inductive expression patterns of antimicrobial peptide genes in the silkworm Bombyx mori. Genomics 2005, 87(2006):356-365.
110. Wang Y, Chen KP, Yao Q, Wang WB, Zhu Z: The basic helix-loop-helix transcription factor family in the honeybee,Bombyx mori.J Insect Science 2008, 8(44):In press.
2.Ma P,Rould M,Weintraub H,Pabo C:Crystal structure of MyoD bHLH domain-DNA complex:perspectives on DNA recognition and implications for transcriptional activation.Cell 1994,77(3):451-459.
3.Murre C,McCaw PS,Baltimore D:A new DNA binding and dimerizing motif in immunoglobulin enhancer binding,Daughterless,MyoD,and Myc proteins.Cell 1989,56:777-783.
4.Simionato E,Ledent V,Richards G,Thomas-Chollier M,Kerner P,Coornaert D,Degnan BM,Vervoort M:Origin and diversification of the basic helix-loop-helix gene family in metazoans:insights from comparative genomics.BMC Evol Biol 2007,7:33.
5.Massari ME,Murre C:Helix-Loop-Helix Proteins:Regulators of Transcription in Eucaryotic Organisms.Mol Cell Biol 2000,20(2):429-440.
6.Jones DT,Taylor WR,Thornton JM:The rapid generation of mutation data matrices from protein sequences.CABIOS 1992,8:275-282.
7.贺强,王立峰:bHLH蛋白家族的功能.国外医学-生理、病理科学与临床分册2004,24(6):545-547.
8.Atchley WR,Fitch WM:A natural classification of the basic helix-loop-helix class of transcription factors.Proc Natl Acad Sci U S A 1997,94(10):5172-5176.
9.Atchley WR,Terhalle W,Dress A:Positional dependence,cliques,and predictive motifs in the bHLH protein domain.J Mol Evol 1999,48(5):501-516.
10.Moore AW,Barbel S,Jan LY,Jan YN:A genomewide survey of basic helix-loop-helix factors in Drosophila.Proc Natl Acad Sci USA 2000,97(19):10436-10441.
11.Ledent V,Vervoort M:The basic helix-loop-helix protein family:comparative genomics and phyiogenetic analysis.Genome Res 2001,11(5):754-770.
12.Ledent V,Paquet O,Vervoort M:Phylogenetic analysis of the human basic helix-loop-helix proteins.Genome Biol 2002,3(6):RESEARCH0030.
13.Satou Y,Imai KS,Levine M,Kohara Y,Rokhsar D,Satoh N:A genomewide survey of developmentally relevant genes in Ciona intestinalis.I.Genes for bHLH transcription factors.Dev Genes Evol 2003,213(5-6):213-221.
14.Wang Y,Chen KP,Yao Q,Wang WB,Zhu Z:The basic helix-loop-helix transcription factor family in Bombyx mori.Dev Genes Evol 2007,217(10):715-723.
15.Alonso MC,Cabrera CV:The achaete-scutegene complex of Drosophila melanogaster comprises four homologous genes.EMBO J 1988,7:2585-2591.
16.CelegansSequencingConsortium:Genome sequence of the nematode C.elegans:a platform for investigating biology. Science 1998, 282(5396):2012-2018.
17. Weintraub H, Dwarki VJ, Verma I, Davis R, Hollenberg S, Snider L, Lassar A, Tapscott SJ: Muscle-specific transcriptional activation by MyoD. Genes Dev 1991, 5(8): 1377-1386.
18. Sommer L, Ma Q, Anderson DJ: neurogenins, a novel family of atonal-related bHLH transcription factors, are putative mammalian neuronal determination genes that reveal progenitor cell heterogeneity in the developing CNS and PNS. Mol Cell Neurosci 1996, 8(4):221-241.
19. Kho CJ, Huggins GS, Endege WO, Patterson C, Jain MK, Lee ME, Haber E: The polymyositis-scleroderma autoantigen interacts with the helix-loop-helix proteins E12 and E47. J Biol Chem 1997, 272(20): 13426-13431.
20. Jarman AP, Grau Y, Jan LY, Jan YN: atonal is a proneural gene that directs chordotonal organ formation in the Drosophila peripheral nervous system. Cell 1993,73(7): 1307-1321.
21. Lemercier C, To RQ, Swanson BJ, Lyons GE, Konieczny SF: Mist1: a novel basic helix-loop-helix transcription factor exhibits a developmentally regulated expression pattern. Dev Biol 1997,182(1): 101-113.
22. Peyton M, Stellrecht CM, Naya FJ, Huang HP, Samora PJ, Tsai MJ: BETA3, a novel helix-loop-helix protein, can act as a negative regulator of BETA2 and MyoD-responsive genes. Mol Cell Biol 1996, 16(2):626-633.
23. Zhou Q, Wang S, Anderson DJ: Identification of a novel family of oligodendrocyte lineage-specific basic helix-loop-helix transcription factors. Neuron 2000, 25(2):331-343.
24. Brentrup D, Lerch H, Jackie H, Noll M: Regulation of Drosophila wing vein patterning: net encodes a bHLH protein repressing rhomboid and is repressed by rhomboid-dependent Egfr signalling. Development 2000, 127(21 ):4729-4741.
25. Armand P, Knapp AC, Hirsch AJ, Wieschaus EF, Cole MD: A novel basic helix-loop-helix protein is expressed in muscle attachment sites of the Drosophila epidermis. Mol Cell Biol 1994, 14(6):4145-4154.
26. Saga Y, Hata N, Kobayashi S, Magnuson T, Seldin MF, Taketo MM: MesP1: a novel basic helix-loop-helix protein expressed in the nascent mesodermal cells during mouse gastrulation. Development 1996, 122(9):2769-2778.
27. Tapanes-Castillo A, Baylies MK: Notch signaling patterns Drosophila mesodermal segments by regulating the bHLH transcription factor twist. Development 2004, 131(10):2359-2372.
28. Burgess R, Cserjesi P, Ligon KL, Olson EN: Paraxis: a basic helix-loop-helix protein expressed in paraxial mesoderm and developing somites. Dev Biol 1995, 168(2):296-306.
29. Lu J, Webb R, Richardson JA, Olson EN: MyoR: a muscle-restricted basic helix-loop-helix transcription factor that antagonizes the actions of MyoD. Proc Natl Acad Sci U S A 1999, 96(2):552-557.
30. Yokota Y, Mori S, Narumi O, Kitajima K: In vivo function of a differentiation inhibitor, Id2. IUBMB Life 2001, 51(4):207-214.
31. Thomas T, Yamagishi H, Overbeek PA, Olson EN, Srivastava D: The bHLH factors, dHAND and eHAND, specify pulmonary and systemic cardiac ventricles independent of left-right sidedness. Dev Biol 1998,196(2):228-236.
32. Knofler M, Krapp A, Hagenbuchle O, Wellauer PK: Constitutive expression of the gene for the cell-specific p48 DNA-binding subunit of pancreas transcription factor 1 in cultured cells is under control of binding sites for transcription factors Sp1 and alphaCbf. J Biol Chem 1996, 271(36):21993-22002.
33. Lecuyer E, Herblot S, Saint-Denis M, Martin R, Begley CG, Porcher C, Orkin SH, Hoang T: The SCL complex regulates c-kit expression in hematopoietic cells through functional interaction with Sp1. Blood 2002,100(7):2430-2440.
34. Chen SL, Dowhan DH, Hosking BM, Muscat GE: The steroid receptor coactivator, GRIP-1, is necessary for MEF-2C-dependent gene expression and skeletal muscle differentiation. Genes Dev 2000, 14(10): 1209-1228.
35. Dean J: Oocyte-specific genes regulate follicle formation, fertility and early mouse development. J Reprod Immunol 2002, 53( 1 -2): 171 -180.
36. Kaddurah-Daouk R, Greene JM, Baldwin ASJ, Kingston RE: Activation and repression of mammalian gene expression by the c-myc protein. Genes Dev 1987, 1(4):347-357.
37. Ayer D, Kretzner L, Eisenman R: Mad: a heterodimeric partner for Max that antagonizes Myc transcriptional activity. Cell 1993, 72(2):211-222.
38. Hurlin P, Queva C, Eisenman R: Mnt, a novel Max-interacting.protein is coexpressed with Myc in prohferatlng cells and mediates repression at Myc binding sites. Genes & Development 1997, 11(1):44-58.
39. Blackwood EM, Eisenman RN: Max: a helix-loop-helix zipper protein that forms a sequence-specific DNA-binding complex with Myc. Science 1991, 251(4998): 1211-1217.
40. Reisman D, Rotter V: The helix-loop-helix containing transcription factor USF binds to and transactivates the promoter of the p53 tumor suppressor gene. Nucleic Acids Res 1993,21(2):345-350.
41. Nobukuni Y, Watanabe A, Takeda K, Skarka H, Tachibana M: Analyses of loss-of-function mutations of the M1TF gene suggest that haploinsufficiency is a cause of Waardenburg syndrome type 2A. Am J Hum Genet 1996,59(1):76-83.
42. Yokoyama C, Wang X, Briggs MR, Admon A, Wu J, Hua X, Goldstein JL, Brown MS: SREBP-1, a basic-helix-loop-helix-leucine zipper protein that controls transcription of the low density lipoprotein receptor gene. Cell 1993, 75(1): 187-197.
43. Hua X, Yokoyama C, Wu J, Briggs MR, Brown MS, Goldstein JL, Wang X: SREBP-2, a second basic-helix-loop-helix-lcucine zipper protein that stimulates transcription by binding to a sterol regulatory element. Proc Natl Acad Sci U S A 1993, 90(24): 11603-11607.
44. Hu YF, Lüscher B, Admon A, Mermod N, Tjian R: Transcription factor AP-4 contains multiple dimerization domains that regulate dimer specificity. Genes Dev 1990, 4(10):1741-1752.
45. Stoeckman AK, Ma L, Towle HC: Mlx is the functional heteromeric partner of the carbohydrate response element-binding protein in glucose regulation of lipogenic enzyme genes. J Biol Chem 2004, 279(15): 15662-15669.
46. Bjerknes M, Cheng H: TCFL4: a gene at 17q21.1 encoding a putative basic helix-loop-helix leucine-zipper transcription factor. Gene 1996,181(1-2):7-11.
47. King DP, Zhao Y, Sangoram AM, Wilsbacher LD, Tanaka M, Antoch MP, Steeves TD, Vitaterna MH, Kornhauser JM, Lowrey PL et al. Positional cloning of the mouse circadian clock gene. Cell 1997, 89(4):641-653.
48. Katzenberg D, Young T, Lin L, Finn L, Mignot E: A human period gene (HPER1) polymorphism is not associated with diurnal preference in normal adults. Psychiatr Genet 1999, 9(2):107-109.
49. Hankinson O: The aryl hydrocarbon receptor complex. Annu Rev Pharmacol Toxicol 1995,35:307-340.
50. Muralidhar MG, Callahan CA, Thomas JB: Single-minded regulation of genes in the embryonic midline of the Drosophila central nervous system. Mech Dev 1993, 41(2-3): 129-138.
51. Wilk R, Weizman I, Shilo BZ: trachealess encodes a bHLH-PAS protein that is an inducer of tracheal cell fates in Drosophila. Genes Dev 1996,10(1):93-102.
52. Liu CJ, Ding B, Wang H, Lengyel P: The MyoD-inducible p204 protein overcomes the inhibition of myoblast differentiation by Id proteins. Mol Cell Biol 2002, 22(9):2893-2905.
53. Ellis HM: Embryonic expression and function of the Drosophiia helix-loop-helix gene, extramacrochaetae. Mech Dev 1994, 47(1):65-72.
54. Leimeister C, Externbrink A, Klamt B, Gessler M: Hey genes: a novel subfamily of hairy-and Enhancer of split related genes specifically expressed during mouse embryogenesis. Mech Dev 1999, 85(1-2): 173-177.
55. Wainwright SM, Ish-Horowicz D: Point mutations in the Drosophila hairy gene demonstrate in vivo requirements for basic, helix-loop-helix, and WRPW domains. Mol Cell Biol 1992, 12(6):2475-2483.
56. Maier D, Marte BM, Schafer W, Yu Y, Preiss A: Drosophila evolution challenges postulated redundancy in the E(spl) gene complex. Proc Natl Acad Sci U S A 1993, 90(12):5464-5468.
57. Crozatier M, Valle D, Dubois L, Ibnsouda S, Vincent A: Collier, a novel regulator of Drosophila head development, is expressed in a single mitotic domain. Curr Biol 1996, 6(6):707-718.
58. Kudrycki K, Stein-Izsak C, Behn C, Grillo M, Akeson R, Margolis FL: Olf-1-binding site: characterization of an olfactory neuron-specific promoter motif. Mol Cell Biol 1993, 13(5):3002-3014.
59. Li X, Duan X, Jiang H, Sun Y, Tang Y, Yuan Z, Guo J, Liang W, Chen L, Yin J et al: Genome-wide analysis of basic/helix-loop-helix transcription factor family in rice and Arabidopsis. Plant Physiol 2006,141(4): 1167-1184.
60. Toledo-Ortiz G, Huq E, Quail PH: The Arabidopsis basic/helix-loop-helix transcription factor family. Plant Cell 2003,15(8): 1749-1770.
61. Buck MJ, Atchley WR: Phylogenetic analysis of plant basic helix-loop-helix proteins. J Mol Evol 2003, 56(6):742-750.
62. Heim MA, Jakoby M, Werber M, Martin C, Weisshaar B, Bailey PC: The basic helix-loop-helix transcription factor family in plants: a genome-wide study of protein structure and functional diversity. Mol Biol Evol 2003, 20(5):735-747.
63. Altschul SF, Madden TL, Sch(a|¨)ffer AA, Zhang J, Zhang Z, Miller W, Lipman DJ: Gapped BLAST and PSI-BLAST: a new generation of protein database search programs. Nucleic Acids Res 1997, 25:3389-3402.
64. Seo S, Kroll KL: Geminin's double life: chromatin connections that regulate transcription at the transition from proliferation to differentiation. Cell Cycle 2006, 5(4):374-379.
65. Fischer A, Gessler M: Delta-Notch—and then? Protein interactions and proposed modes of repression by Hes and Hey bHLH factors. Nucleic Acids Res 2007, 35(14):4583-4596.
66. Xia Q, Zhou Z, Lu C, Cheng D, Dai F, Li B, Zhao P, Zha X, Cheng T, Chai C et al: A draft sequence for the genome of the domesticated silkworm (Bombyx mori). Science 2004, 306(5703): 1937-1940.
67. Swofford DL: PAUP* Phylogenetic Analysis Using Parsimony, Version 4. Sinauer Associates, Sunderland, Massachusetts 1998.
68. Kuzoff RK: http://paup.csit.fsu.edu/nfiles.html. 1978.
69. Schmidt HA, K. Strimmer, M. Vingron, and A. von Haeseler TREE-PUZZLE: maximum likelihood phylogenetic analysis using quartets and parallel computing. Bioinformatics 2002, 18:502-504.
70. Tamura K, Dudley J, Nei M, Kumar S: MEGA4: Molecular Evolutionary Genetics Analysis (MEGA) Software Version 4.0. Mol Biol Evol 2007, 24(8): 1596-1599.
71. Nicholas KB, Nicholas-Jr HB, Deerfield-II DW: GeneDoc: Analysis and Visualization of Genetic Variation. Embnet News 1997, 4:14.
72. Fitch W: Distinguishing homologous from analogous proteins. Syst Zool 1970, 19:99-113.
73. Markova EP, Ueda H, Sakamoto K, Oishi K, Shimada T, Takeda M: Cloning of Cyc (Bmal1) homolog in Bombyx mori: structural analysis and tissue specific distributions. Comp Biochem Physiol B Biochem Mol Biol 2003, 134(3):535-542.
74. Matsunami K, Kokubo H, Ohno K, Xu P, Ueno K, Suzuki Y: Embryonic silk gland development in Bombyx: molecular cloning and expression of the Bombyx trachealess gene. Dev Genes Evol 1999, 209:507-514.
75. Zelzer E, Wappner P, Shilo B-Z: The PAS domain confers target gene specificity of Drosophila bHLH/PAS proteins. Genes Dev 1997, 11(16):2079-2089.
76. Lapan S, 王勇: An introduction to molecular biology wich Chinese translation. 化学工业出版社 2008:106.
77. Koonin E: The origin of introns and their role in eukaryogenesis: a compromise solution to the introns-early versus introns-late debate? Biol Direct 2006, 10.1186( 1745-6150): 1 -22.
78. Nguyen H, Yoshihama M, Kenmochi N: Phase distribution of spliceosomal introns: implications for intron origin. BMC Evol Biol 2006, 6:69-78.
79. Cubas P, deCelis J, Campuzano S, Modolell J: Proneural clusters of achaete-scute expression and the generation of sensory organs in the Drosophila imaginal wing disc. Genes Dev 1991, 5(996-1008):996.
80. Skeath J, Carroll S: Regulation of achaete-scute gene expression and sensory organ pattern formation in the Drosophila wing. Genes Dev 1991, 5:984-995.
81. Jan Y, Jan L: Genetic control of cell fate specification in Drosophila peripheral nervous system. Annu Rev Genet 1994, 28:373-393.
82. Wheeler S, Carrico M, Wilson B, Brown S, Skeath J: The expression and function of the achaete-scute genes in Tribolium castaneum reveals conservation and variation in neural pattern formation and cell fate specification. Development 2003,130(18):4373-4381.
83. Takano T: Rate variation of DNA sequence evolution in the Drosophila lineages. Genetics Genetics, 149(2):959-970.
84. Carmena A, Bate M, Jimenez F: Lethal of scute, a proneural gene, participates in the specification of muscle progenitors during Drosophila embryogenesis. Genes Dev 1995, 9(19):2373-2383.
85. Grillenzoni N, de Vaux V, Meuwly J, Vuichard S, Jarman A, Holohan E, Gendre N, Stacker RF: Role of proneural genes in the formation of the larval olfactory organ of Drosophila. Dev Genes Evol 2007, 217(3):209-219.
86. Goulding S, White N, Jarman A: cato encodes a basic helix-loop-helix transcription factor implicated in the correct differentiation of Drosophila sense organs. Dev Biol 2000, 221(1): 120-131.
87. Jarman A, Sun Y, Jan L, Jan Y: Role of the proneural gene, atonal, in formation of Drosophila chordotonal organs and photoreceptors. Development 1995, 121(7):2019-2030.
88. zur Lage PI, Prentice DR, Holohan EE, Jarman AP: The Drosophila proneural gene amos promotes olfactory sensillum formation and suppresses bristle formation. Development 2003,130(19):4683-4693.
89. Kim MH, Gunnersen J, Augustine C, Tan SS: Region-specific expression of the helix-loop-helix gene BETA3 in developing and adult brains. Mech Dev 2002, 114(1-2):125-128.
90. Morimoto M, Kiso M, Sasaki N, Saga Y: Cooperative Mesp activity is required for normal somitogenesis along the anterior-posterior axis. Dev Biol 2006,300(2):687-698.
91. Castanon I, Von Stetina S, Kass J, Baylies MK: Dimerization partners determine the activity of the Twist bHLH protein during Drosophila mesoderm development. Development 2001, 128(16):3145-3159.
92. Spicer D, Rhee J, Cheung W, Lassar A: Inhibition of myogenic bHLH and MEF2 transcription factors by the bHLH protein twist. Science 1996, 272:1476-1480.
93. Hamamori Y, Wu HY, Sartorelli V, Kedes L: he basic domain of myogenic basic helix-loop-helix (bHLH) proteins is the novel target for direct inhibition by another bHLH protein, Twist. Mol Cell Biol 1997,17:6563-6573.
94. Yu L, Sangster N, Perez A, McCormick PJ: The bHLH protein MyoR inhibits the differentiation of early embryonic endoderm. Differentiation 2004, 72(7):341-347.
95. Facchini L, Penn L: The molecular role of Myc in growth and transformation: recent discoveries lead to new insights. FASEB J 1998,12:633-651.
96. Henriksson M, Luscher B: Proteins of the Myc network: essential regulators of cell growth and differentiation. Adv Cancer Res 1996, 68:109-182.
97. Cheng S, Davies K, Yung E, Beltran R, Yu J, Kalpana G: c-MYC interacts with INI1/hSNF5 and requires the SWI/SNF complex for transactivation function. Nat Genet 1999,22:102-105.
98. Cole M: The affairs of daughterless and the promiscuity of developmental regulators. Cell 1989,59:231-234.
99. McMahon S, VanBuskirk H, Dugan K, Copeland T, Cole M: The novel ATM-related protein TRRAP is an essential cofactor for the c-Myc and E2F oncoproteins. Cell 1998, 94:363-374.
100. Jung H, Kim K, Chung Y, Chung H, Min Y, Lee M, Lee M, Kim K, Chung J: USF inhibits cell proliferation through delay in G2/M phase in FRTL-5 cells. Endocr J 2007, 54(2):275-285.
101. Sirito M, Walker S, Lin Q, Kozlowski M, Klein W, Sawadogo M: Members of the USF family of helix-loop-helix proteins bind DNA as homo- as well as heterodimers. Gene Expr 1992, 2(3):231-240.
102. Langlands K, Yin X, Anand G, Prochownik E: Differential interactions of Id proteins with basic-helix-loop-helix transcription factors. J Biol Chem 1997,272:19785-19793.
103. Yan W, Young A, Soares V, Kelley R, Benezra R, Zhuang Y: High incidence of T-cell tumors in E2A-null mice and E2A/Idl double-knockout mice. Mol Cell Biol 1997, 17:7317-7327.
104. Yokota Y, Mansouri A, Mori S, Sugawara S, Adachi S, Nishikawa S, Gruss P: Development of peripheral lymphoid organs and natural killer cells depends on the helix-loop-helix inhibitor Id2. Nature 1999, 397:702-706.
105. Jen Y, Manova K, Benezra R: Expression patterns of Id1, Id2, and Id3 are highly related but distinct from that of Id4 during mouse embryogenesis. Dev Dyn 1996, 207(3):235-252.
106. Yokota Y, Mori S: Role of Id family proteins in growth control. J Cell Physiol 2002, 190(1):21-28.
107. Baonza A, Garcia-Bellido A: Dual role of extramacrochaetae in cell proliferation and cell differentiation during wing morphogenesis in Drosophila. Mech Dev 1999, 80(2): 133-146.
108. Campuzano S: Emc, a negative HLH regulator with multiple functions in Drosophila development. Oncogene 2001, 20(58):8299-8307.
109. Cheng T, Zhao P, Liu C, Xu P, Gao Z, Xia Q, Xiang Z: Structures, regulatory regions, and inductive expression patterns of antimicrobial peptide genes in the silkworm Bombyx mori. Genomics 2005, 87(2006):356-365.
110. Wang Y, Chen KP, Yao Q, Wang WB, Zhu Z: The basic helix-loop-helix transcription factor family in the honeybee,Bombyx mori.J Insect Science 2008, 8(44):In press.