烟草核基质结合序列在转基因遗传稳定性中的功能及机理分析
|
摘要
目前通过植物转基因技术进行作物品种的改良已经成为作物品质改良的重要手段。我们都希望外源转入的优良基因能在作物中得到高效和稳定的表达,但是外源的基因在转入植物中一代或者几代后会出现不再表达、表达变弱的现象。这种现象的发生很大程度上是由于转基因沉默现象导致的。由于转基因沉默严重阻碍转基因商品化的进程,因此,如何提高转基因后代的遗传稳定性、减少转基因沉默的发生是一个亟待解决的问题。
核基质结合区(Matrix Attachment Regions,MARs)是基因组上通常富含A/T的能够将DNA或染色质附着到核基质上的DNA序列。通过与结合蛋白的互作,MARs在维持或修饰DNA或染色质结构及调控相关基因方面表达中发挥重要作用。以往的研究者发现核基质结合序列在减少转基因沉默方面具有重要作用。
TM6是本实验室从烟草核基质中分离得到的一个具有一般MARs结构特征的DNA序列,核基质体外结合实验证明TM6与烟草核基质具有很强的体外结合能力。为了研究TM6在植物体内的功能,主要是在其提高转基因后代遗传稳定性中的作用,我们构建不同的植物表达载体并转化了双子叶植物烟草和拟南芥,对转基因植株中TM6连接的外源基因的表达情况进行了分析。为了进一步研究TM6的作用机理,本实验还分析了TM6对其邻近启动子区域DNA甲基化的影响,主要实验结果如下:
1.在双子叶植物烟草中,双TM6能够明显的降低杂交后代的转基因沉默比例,提高转基因后代的遗传稳定性。这个实验结果为TM6在提高外源基因在转基因植物中的遗传稳定性方面的应用提供了实验依据。
2.烟草TM6序列能够显著提高侧翼启动子区对核酸酶的敏感性。在DNaseI处理后的转TM6的转基因烟草细胞核内,TM6显著降低了CaMV35S启动子区域的特异扩增水平,初步说明TM6能够减低其邻近启动子区域DNA甲基化水平,从而降低基因沉默的发生,提高基因表达。
3.对转基因烟草中CaMV35S和NOS启动子区域的DNA甲基化程度进行检测,分析得知:在CaMV35S启动子区域,没有TM6的转基因烟草植株的DNA甲基化水平较高大约在13%～37%,而有TM6的转基因烟草植株中几乎没有DNA甲基化的发生;在NOS启动子区域,没有TM6的转基因烟草植株的DNA甲基化水平较高大约在24%～51%,而有TM6的转基因烟草植株的DNA甲基化水平在9%～14%左右。该实验进一步验证了TM6能够显著降低其邻近启动子区域DNA甲基化水平。
4.双子叶植物烟草中分离的TM6同样可以在拟南芥中增强外源基因的表达,并且在不同类型的启动子(组成型35S启动子、冷诱导型COR启动子和光合组织特异型启动子PNZIP启动子)的驱动下都能有增强表达的作用。说明TM6是一个能广泛提高外源目的基因表达的核基质结合序列,并且这种对外源基因表达的提高并不改变启动子的作用类型。
Gene transfer technology is becoming a fundamental tool to enhance agronomic performance or improve quality traits in a wide variety of crop species. But gene transfer technology are sometimes severely handicapped by transgene silencing and instability of gene expression. Transgene expression is frequently lost after one or a few sexual generations. So it is important to adopt efficient strategies to overcome gene silencing and increase transgene expression level for optimizing transgenic technology.
Matrix Attachment Regions (MARs) are the DNA sequences with rich A/T nucleotides that may be involved in anchoring DNA/chromatin to the nuclear matrix. By the interaction with the binding proteins, MARs play an important role in the maintance and modification of the DNA/chromatin structure and the regulation of the gene expression. They have been seen as fundamental tools to reduce or eliminate some forms of transgene silencing because of their capacity to increase transgene expression levels or reduce the variance between transgenic events when flanking a transgene cassette in both plants and animals.
TM6 is a matrix attachment region isolated from the genomic DNA of tobacco, which can strongly bind to the tobacco nuclear matrix in vitro. In this study, we investigated the effect of TM6 on stability of transgene expression in the progeny of the primary stably transformed tobacco and the function of TM6 in Arabidopsis. We also investigated the effect of TM6 on the DNA methylation status of promoter regions. The main results were as follows:
1. TM6 can decrease transgene silence of backcross progeny in tobacco, and increase stability of transgene expression in the progeny of the primary tansformed tobacco. This results make it possible for the application of TM6 in transgene plants to increase stability of transgene expression.
2. According to the DNaseI accessibility analysis, the CaMV35S promoter adjacent to the TM6 is degraded more rapidly than the control without MAR. Considering the increasing accessibility to DNaseI would result in the decrease of PCR products for the regions of interest, the difference reveals that TM6 plays a role in decreasing DNA methylation of the promoter regions. This maybe one mechanism of TM6 decrease transgene silence and increase gene expression.
3. we also detect DNA methylation status of the CaMV35S region and NOS region in transformed tobacco with and without TM6. In our results, there is almost no DNA methylation of CaMV35S regions in transformed tobacco with TM6 but there is 13%～37% DNA methylation of CaMV35S regions in transformed tobacco without TM6. In NOS region, frequence of DNA methylation is 24%～51% in transformed tobacco with TM6 compared 9%～14% those without TM6. This results indicate that TM6 can decrease the DNA methylation in both CaMV35S regions and NOS regions.
4. Although TM6 is isolated from tobacco, it can also enhance transgene expression in arabidopsis. We use different type promoters (CaMV35S, PNZIP, COR) to test the influence of TM6 in transgenic arabidopsis, and find that TM6 can enhance gene expression in the transgenic Arabidopsis with three promoters. This indicated TM6 can widely enhance gene expression in different kinds of plants, not change the gene expression pattern.
核基质结合区(Matrix Attachment Regions,MARs)是基因组上通常富含A/T的能够将DNA或染色质附着到核基质上的DNA序列。通过与结合蛋白的互作,MARs在维持或修饰DNA或染色质结构及调控相关基因方面表达中发挥重要作用。以往的研究者发现核基质结合序列在减少转基因沉默方面具有重要作用。
TM6是本实验室从烟草核基质中分离得到的一个具有一般MARs结构特征的DNA序列,核基质体外结合实验证明TM6与烟草核基质具有很强的体外结合能力。为了研究TM6在植物体内的功能,主要是在其提高转基因后代遗传稳定性中的作用,我们构建不同的植物表达载体并转化了双子叶植物烟草和拟南芥,对转基因植株中TM6连接的外源基因的表达情况进行了分析。为了进一步研究TM6的作用机理,本实验还分析了TM6对其邻近启动子区域DNA甲基化的影响,主要实验结果如下:
1.在双子叶植物烟草中,双TM6能够明显的降低杂交后代的转基因沉默比例,提高转基因后代的遗传稳定性。这个实验结果为TM6在提高外源基因在转基因植物中的遗传稳定性方面的应用提供了实验依据。
2.烟草TM6序列能够显著提高侧翼启动子区对核酸酶的敏感性。在DNaseI处理后的转TM6的转基因烟草细胞核内,TM6显著降低了CaMV35S启动子区域的特异扩增水平,初步说明TM6能够减低其邻近启动子区域DNA甲基化水平,从而降低基因沉默的发生,提高基因表达。
3.对转基因烟草中CaMV35S和NOS启动子区域的DNA甲基化程度进行检测,分析得知:在CaMV35S启动子区域,没有TM6的转基因烟草植株的DNA甲基化水平较高大约在13%～37%,而有TM6的转基因烟草植株中几乎没有DNA甲基化的发生;在NOS启动子区域,没有TM6的转基因烟草植株的DNA甲基化水平较高大约在24%～51%,而有TM6的转基因烟草植株的DNA甲基化水平在9%～14%左右。该实验进一步验证了TM6能够显著降低其邻近启动子区域DNA甲基化水平。
4.双子叶植物烟草中分离的TM6同样可以在拟南芥中增强外源基因的表达,并且在不同类型的启动子(组成型35S启动子、冷诱导型COR启动子和光合组织特异型启动子PNZIP启动子)的驱动下都能有增强表达的作用。说明TM6是一个能广泛提高外源目的基因表达的核基质结合序列,并且这种对外源基因表达的提高并不改变启动子的作用类型。
Gene transfer technology is becoming a fundamental tool to enhance agronomic performance or improve quality traits in a wide variety of crop species. But gene transfer technology are sometimes severely handicapped by transgene silencing and instability of gene expression. Transgene expression is frequently lost after one or a few sexual generations. So it is important to adopt efficient strategies to overcome gene silencing and increase transgene expression level for optimizing transgenic technology.
Matrix Attachment Regions (MARs) are the DNA sequences with rich A/T nucleotides that may be involved in anchoring DNA/chromatin to the nuclear matrix. By the interaction with the binding proteins, MARs play an important role in the maintance and modification of the DNA/chromatin structure and the regulation of the gene expression. They have been seen as fundamental tools to reduce or eliminate some forms of transgene silencing because of their capacity to increase transgene expression levels or reduce the variance between transgenic events when flanking a transgene cassette in both plants and animals.
TM6 is a matrix attachment region isolated from the genomic DNA of tobacco, which can strongly bind to the tobacco nuclear matrix in vitro. In this study, we investigated the effect of TM6 on stability of transgene expression in the progeny of the primary stably transformed tobacco and the function of TM6 in Arabidopsis. We also investigated the effect of TM6 on the DNA methylation status of promoter regions. The main results were as follows:
1. TM6 can decrease transgene silence of backcross progeny in tobacco, and increase stability of transgene expression in the progeny of the primary tansformed tobacco. This results make it possible for the application of TM6 in transgene plants to increase stability of transgene expression.
2. According to the DNaseI accessibility analysis, the CaMV35S promoter adjacent to the TM6 is degraded more rapidly than the control without MAR. Considering the increasing accessibility to DNaseI would result in the decrease of PCR products for the regions of interest, the difference reveals that TM6 plays a role in decreasing DNA methylation of the promoter regions. This maybe one mechanism of TM6 decrease transgene silence and increase gene expression.
3. we also detect DNA methylation status of the CaMV35S region and NOS region in transformed tobacco with and without TM6. In our results, there is almost no DNA methylation of CaMV35S regions in transformed tobacco with TM6 but there is 13%～37% DNA methylation of CaMV35S regions in transformed tobacco without TM6. In NOS region, frequence of DNA methylation is 24%～51% in transformed tobacco with TM6 compared 9%～14% those without TM6. This results indicate that TM6 can decrease the DNA methylation in both CaMV35S regions and NOS regions.
4. Although TM6 is isolated from tobacco, it can also enhance transgene expression in arabidopsis. We use different type promoters (CaMV35S, PNZIP, COR) to test the influence of TM6 in transgenic arabidopsis, and find that TM6 can enhance gene expression in the transgenic Arabidopsis with three promoters. This indicated TM6 can widely enhance gene expression in different kinds of plants, not change the gene expression pattern.
引文
1.杨予涛,杨国栋,刘石娟,郭兴启,郑成超。一个光合组织特异表达强启动子的分离及功能分析。2003,30:298~306。
2.张可伟,王健美,杨国栋,郭兴启,温孚江,崔德才,郑成超。强MAR的分离及其体内外功能鉴定。科学通报,2002,47:1527~1577.
3. Aenisch R, Bird A. Epigenetic regulation of gene expression: how the genome integrates intrinsic and environmential signals. Nat Genet, 2003, 33:245~254
4. Aufsatz W, Mette MF, Winden J, Matzke AJM, Matzke M. RNA directed DNA methylation in Arabidopsis. Proc Natl Acad Sci USA, 2002, 16(Suppl.)4: 499~506
5. Allen GC, Hall G Jr, Michalowski S, Newman W, Spiker S, Weissinger AK, Thompson WF. High-level transgene expression in plant cells: effects of a strong scaffold attachment region from tobacco. Plant Cell, 1996, 8:899~913
6. Allen G A, Hall G E Jr, Childs L C. Scaffold-attached regions increase reporter gene expression in stably transformed plant cells. Plant Cell, 1993, 5:603~613
7. Allen G C, Hall G E Jr, Michalowski S et al. High-level transgene expression in plant cells; effect of a strong scaffold attachment region from tabacoo. Plant Cell, 1996, 8:899~913
8. Antes TJ, Namicu SJ, Fournier RE and Levy-Wilson B. The 5′- boundary of the human apolipoprotein B chromatin domain in intestinal cells. Biochemistry, 2001, 40:6731~6742
9. Anandalakshmi R, Pruss G J, Ge X et al. A viral suppressor of genesilencing in plants. Proc. Natl. Acad. Sci. USA, 1998, 95: 13079 ~13084.
10. Allen GC, Spiker S, Thompson W F. Use of matrix attachment regions (MARs) to minimize transgene silencing. Plant Mol Biol, 2000, 43: 361~376
11. Adachi Y, Kas E, Laemmli UK. Preferential, cooperative binding of DNA topoisomerase II to scaffold-associated regions. EMBO J, 1989, 8:3997~4006
12. Alvarez J D, Yasui DH, Niida H, Joh T, Loh DY, and Kohwi- Shigematsu T. The MAR-binding protein SATB1 orchestrates temporal and spatial expression of multiple genes during T-cell development. Genes & Dev, 2000, 14: 521~535
13. Baroux C, Spillane C, Grossniklaus U. Genomic imprinting during seed development. Adv Genet Academic Press San Diego USA, 2002: 165 ~214.
14. Bender J. DNA methylation and epigenetics. Annu Rev Plant Biol, 2004, 55: 41~68
15. Bestor TH. The DNA methyltransferases of mammals. Hum Mol Genet, 2000, 9: 2395~2402
16. Bartee L, Malagnac F, Bender J. Arabidopsis cmt3 chromomethylase mutations block non-CG methylation and silencing of an endogenous gene. Genes Dev, 2001, 15: 1753~1758.
17. Brzeski J, Jerzmanowski A. Deficient in DNA methylation 1 (DDM1) defines a novel family of chromatin remodling factors. J Biol Chem, 2003, 278: 823~828.
18. Bartee L, Bender J. Two Arabidopsis methylation- deficiency mutations confer only partial effects on a methylated endogenous gene family. Nucleic Acids Res, 2001, 29: 2127~2134
19. Burn J E, Bagnall D J, Metzger J D, et al. DNA methylation, vernalization, and the initiation of flowering. Proc Natl Acad Sci USA, 1993, 90:287~ 291.
20. Buryanov YI, Shevchuk TV. DNA methyltransferases and structural-functional specificity of eukaryotic DNA modification. Biochemistry (Moscow), 2005, 70:730~742
21. Berezney R and Coffey DS. Identification of a nuclear protein matrix. Biochem Biophys Res Commun, 1974, 60:1410~1470
22. Breyne P, Van Montagu M, Depicker A, et al. Characterization of a plant scaffold attachment region in a DNA fragment that normalizes transgene expression in tobacco. Plant Cell, 1992, 4:463~471.
23. Bode J, Kohwi Y, Dickinson L et al. Biological significance of unwinding capabiliyu of nuclear matrix-associating DNAs. Science, 1992, 255:195~197
24. Breyne P, Van Montagu M, Gheysen G. The role of scaffold attachment region in the structural and functional organization of plant chromatin. Transgenic Res, 1994, 3:195~202.
25. Benham C, Kohwi-Shigematsu T, Bode J. Stressinducedduplex DNA destabilization in scaffold/matrix attachment regions. J. Mol. Biol. 1997, 274:181~196
26. Brouwer C, Bruce W, Maddock S, et al. Suppression of transgnene silencing by matrix attachment regions in maize: a dual role for the maize 5′ADH1 matrix attachment region. Plant cell, 2002, 14:2251 ~2264
27. Brigneti G, Voinnet O, Li W X, et al. Viral pathogenicity deterants are suppressors of transgene silencing in Nicotiana benthamiana. EMBO J. 1998, 17: 6739~6746
28. Belshaw NJ, Hakola S, Nevalanien, Penttil? M, Suominen P, Archer DB. Trichoderma reesei sequences that bind to the nuclear matrix enhance transformation frequency. Mol. Gen. Genet, 1997, 256: 18~27
29. Berezney R and Coffey DS. Identification of a nuclear protein matrix. Biochem Biophys Res Commun, 1974, 60:1410~1470
30. Bianchi ME, Agresti A. HMG proteins: Dynamic players in gene regulation and differentiation. Curr Opin Genet Dev, 2005, 15: 496~506
31. Bird A, 2002, DNA methylation patterns and epigenetic memory, Genes Dec. 16:6~21
32. Cao X, Springer NM, Muszynski MG, Phillips RL, Kaeppler S, Jacobsen SE. Conserved plant genes with similarity to mammalian de novo DNA methyltransferases. Proc Natl Acad Sci USA, 2000 97: 4979~4984.
33. Cao X, Jacobsen SE. Role of the Arabidopsis DRM methyltransferases in de novo DNA methylation and gene silencing. Curr Biol, 2002, 12: 1138~1144.
34. Chan SW, Zilberman D, Xie Z, Johansen LK, Carrington JC, Jacobsen SE. RNA silencing genes control de novo DNA methylation. Science, 2004, 303:1336
35. Cao X, Aufsatz W, Zilberman D, Mette MF, Huang MS, Matzke M, Jacobsen SE. Role of the DRM and CMT3 methyltransferases in RNA-directed DNA methylation. Curr Biol, 2003, 13: 2212~2217.
36. Curradi M, Izzo A, Badaracco G, et al. Molecular Mechanisms of Gene Silencing Mediated by DNA Methylation. Mol Cell Biol, 2002, 22:3157~3173
37. Chan SW, Henderson IR, Jacobsen SE. Gardening the genome: DNA methylation in Arabidopsis thaliana. Nature Publishing Group, 2005, 6:351~360.
38. Chan SW, Zilberman D, Xie Z, Johansen LK, Carringtion JC, Jacobsen SE. RNA silencing genes control de novo DNA methylation. Science, 2004, 303:1336~1336.
39. Cogon C, Macimo G. Gene silencing in Macrospore crassa requires a protein homologous to RNA-dependent RNA polymerase. Nature, 1999, 399:166~168.
40. Chinnusamy V, Ohta M, Kanrar S, Lee BH, Hong X, Agarwal M, Zhu JK. ICE1: a regulator of cold-induced transcriptome and freezing tolerance in Arabidopsis Genes Dev. 2003, 17: 1043~1054.
41. Cockerill PN, Garrard WT. Chromosomal loop anchorage of the kappa immunoglobulin gene occurs next to the enhancer in a region containing topoisomeraseⅡsites. Cell, 1986, 44:273~282.
42. Cornelis M. Van Drunen, Oosterling R W, Keultjes G M et al. Analysis of the chromatin domain organization around the plastocyanin gene reveals an MARs-specific sequence element in Arabidopsis thalami. Nucleic Acids Research, 1997, 25:3904~3911
43. Dijlwell PA, Hamlin JL. Matrix attachment regions are positioned near replication initiation sites, gene, and an interam plicon junction in the amplified dihydrofolate reductase domain of Chinese hamster ovary cell. Mol Cell Biol, 1988, 8:5398~5409.
44. Dietz A, Kay V, Schlacker T, Landsmann J and Bode J. A plant scaffold attached region detected close to a T-DNA integration site is active in mammalian cells. Nucleic Acids Res, 1994, 22: 2744~2751
45. Dickinson LA, Kohwi-Shigematsu T. Nucleolin is a matrix attachment region DNA-binding protein that specifically recognizes a region with high base-unpairing potential. Mol Cell Biol, 1995, 15: 456~465
46. Dobreva G, Dambacher J, Grosschedl R. SUMO modification of a novel MAR-binding protein, SATB2, modulates immunoglobulin mu gene expression. Genes Dev, 2003, 17:3048~ 3061
47. Eads CA, Danenberg KD, Kawakami K, Saltz LB, Blake C, Shibata D, Danenberg PV, Elmavan T, Proux F, Vaucheret H. Arabidopsis RPA2: a genetic link among transcriptional gene silencing, DNA repair, and DNA replication. Curr Biol, 2005, 15: 1919~1925
48. Finnegan E J, Genger R K, Kovac K, et al. DNA methylation and the promotion of flowering by vernalization. Proc Naitl Acad Sci USA, 1998, 95:5824~ 5829
49. Fagard M, Vaucheret H. (Trans) Gene silencing in plants: how many mechanisms? Annu Rev Plant Physiol Plant Mol Biol, 2000, 51: 167~ 194
50. Fujiwara S, Matsuda N, Sato T, et al. Molecular properties of a matrix attachment region~binding protein located in the nucleoli of tobacco cells. Plant Cell Physiol, 2002, 43:1558~1567
51. Fackelmayer F O, Dahm K, Renz A et al. Nucleic-acid-binding property -es of hnRNP-U/SAF-A, a nuclear-matrix protein which binds DNA and RNA in vivo and in vitro. Eur. J. Biochem. 1994, 211: 747~ 757
52. Fackelmayer F O and Richter A. Purification of two isoforms of hnRNP -U and characterization of their nucleic acid binding activity. Biochemis -try, 1994, 33:10416~10422
53. Fackelmayer FO, Dahm K, Renz A, Ramsperger U, Richter A. Nucleic -acid-binding properties of hnRNP-U/SAF-A, a nuclear -matrix protein which binds DNA and RNA in vivo and in vitro. Eur J Biochem, 1994, 221:749~7
54. Fujimoto S, Matsunaga S, Yonemura M, Uchiyama S, Azuma T, Fukui K. Identification of a novel plant MAR DNA binding protein localized on chromosomal surfaces. Plant Mol Biol, 2004, 56:225~239
55. Gruenbaum Y, Naveh MT, Cedar H, Razin A. Sequence specificity of methylation in higher plant DNA. Nature, 1981, 292: 860~862
56. Gheysen G, Montagu M V and Zambryski P. Integration of Agrobact- erium tumefaciens transfer DNA (T-DNA) involves rearrangements of target plant DNA sequences. Proc. Natl Acad. Sci. USA, 1987, 84: 6169 ~6173
57. Gasser S M, Laemmli U K. The organization of chromatin loops: characterization of scaffold attachment sites. EMBO, 1986, 5:511~518
58. Gohring F and Fackelmayer. The scaffold/matrix attachment region binding protein hnRNP-U (SAF-A) is directly bound to chromosomalDNA in vivo: a chemical cross-linking study. Biochemistry, 1997, 36: 8276~8283
59. Grasser KD, Launholt D. Chromatin-associated architectural HMGA and HMGB proteins assist transcription factor function. In Regulation of Transcription in Plants, K. D. Grasser, ed. (Oxford, UK: Blackwell Publishing) Plant Physiol, 2006, 54~78
60. Henikoff S, Comai L. A DNA methyltransferase homolog with a chrom -odomain exists in multiple polymorphic forms in Arabidopsis. Genetic -s, 1998, 149: 307~318.
61. Hall G E, Jr, Allen G C, et al. Nuclear scaffolds and scaffold–attachme -nt regions in higher plants. Proc. Natl. Acad. Sci. USA, 1991. 88: 9320 ~9324.
62. Holmes-Davis R, Comai L. The matrix attachment regions (MARs) associated with the Heat Shock Cognate 80 gene (HSC80) of tomato represent specific regulatory elements. Mol Genet Genomics, 2002, 266:891~898
63. Hua Xue, Yu-TaoYang, Chang-AiWu, Guo-Dong Yang, Cheng-Chao Zheng. TM2, a novel strong matrix attachment region isolated from tobacco, increases transgene expression in transgenic rice calli and plants, Theor. Appl. Genet. 2005, 110: 620~627
64. Izaurralde E, Kas E, Laemmli UK. Highly preferential nude H1 assemb -ly on sacffold-associated regions. J Mol Biol, 1989, 210: 573~585
65. Jacobsen SE, Meyerowitz EM. Hypermethylated SUPERMAN epigene -tic alleles in Arabidopsis. Science, 1997, 277: 1100~1103
66. Johns EW. The HMG Chromosomal Proteins. Academic Press, 1982, London
67. Jeong SY, Peffer N, Meier I. Phosphorylation by protein kinase CKII modulates the DNA-binding activity of a chloroplast nucleoid-associate -ed protein. Planta, 2004, 219:298~302
68. Jackson D A. Chromatin domains and nuclear compartments: establish -ing sites of gene expression in eukaryotic nuclei. Mol Biol Rep 1997, 24: 209~220
69. Jackson D A, Dickinson P and Cook P R. Attachment of DNA to the nucleoskeleton of HeLa cells examined using physiological conditions. Nucl. Acids Res. 1990a. 18: 4385~4393
70. Kass SU, Pruss D, Wolffe AP, et al. How does DNAmethylation repress transcription? Trens genet, 1997, 13:444~449
71. Klose R J, Bird A P. Genomic DNA methylation:the mark and its media -tors. Trends Biochem Sci, 2006, 31:89~ 97
72. Kozak M. Point mutations define a sequence flanking the AUG initiator codon that modulates translation by eukaryotic ribosomes. Cell, 1986, 44: 283~292
73. Kas E, Lzaurralde E K, Laemmli U K. Highly preferential nucleation of histone H1 assembly on scaffold-associated regions. Mol. Biol. 1989, 210:587~599
74. Kas E, Lzaurralde E K, Laemmli U K. Specific inhibition of DNA binding to nuclear scaffolds and histone H1 by distamycin. Mol. Biol. 1989, 210:573~585
75. Kas E and Chasin L A. Anchorage of the Chinese hamster dihydrofolate reductase gene to the nuclear scaffold occurs in an intragenic region. Mol. Biol, 1987, 198:677~692
76. Kas E, Plojak L, Adachi Y et al. A model for chromatin opening: stimulation of topoisomeraseⅡand restriction enzyme cleavage of chromatin by histaminic. EMBO, 1993, 12:115~126
77. Kipp MF, Gohriong T, Ostendorp CM. SAF-Box, a conserved protein domain that specifically recognizes scaffold attachment region DNA. Mol. Cell. Biol. 2000, 20:7480~7489
78. Kohwi-Shigematsu T, Maass K, and Bode J. (1997) Athymocyte factor SATB1 suppresses transcription of stably integrated matrix - attachment region-linked reporter genes. Biochemistry 36: 12005 ~12010
79. Kiledjian M, and Dreyfuss G. Primary structure and binding activity of the hnRNP U protein: binding RNA through RGG box. EMBO J, 1992, 11:2655~2664
80. Kipp M, Gohring F, Ostendorp T, van Drunen CM, van Driel R, Przybylski M, Fackelmayer FO. SAF-Box, a conserved protein domain that specifically recognizes scaffold attachment region DNA. Mol Cell Biol, 2000, 20:7480~7489
81. Lindroth AM, Cao X, Jackson JP, Zilberman D, McCallum CM, Heniko -ff S, Jacobsen SE. Requirement of CHROMOMETHYLASE3 for main -tenance of CpXpG methylation. Science, 2001, 292: 2077~2080
82. Lichtenstein M, Bergmany C H. B-cell-specific demethylation: A novel role for the intronic chain enhance sequence. Cell, 1994, 1: 913~923
83. Lzaurralde E, Mirkovitch J, Laemmli UK. Interaction of DNA with nuclear scaffolds in vitro. J Mol. Biol, 1988, 200:111~125
84. Ludérus M E, den Blaauwen J L, Smit O J B et al. Binding of matrix attachment regions to lamin polymers involves single-stranded regions and the minor groove. Mol. Cell. Biol. 1994, 14:6297~6305
85. Ludérus M E, A de Graaf, Mattia E et al. Binding of matrix attachment regions to lamin B1. Cell, 1992, 70:949~959
86. Liu WM, Guerra-Vladusic FK, Kurakata S, Lupu R, Kohwi-Shigematsu T. HMG-I(Y) recognizes base-unpairing regions of matrix attachment sequences and its increased expression is directly linked to metastatic breast cancer phenotype. Cancer Res, 1999, 59: 5695~ 5703
87. Levine, A, A. Yeivin, E. Ben Asher, Y. Aloni, and A. Razin. 1993. His -tone H1-mediated inhibition of transcription initiation of methylated te -mplates in vitro. J. Biol. Chem. 268:21754~21759.
88. Malagnac F, Bartee L, Bender J. An Arabidopsis SET domain protein required for maintenance but not estab lishment of DNA methylation. EMBO J, 2002, 21: 6842~6852
89. Michael McArthur and Jean O. Thomas, A preference of histone Hi for methylated DNA, 1996, The EMBO Journal vol. 15 no. 7 Plant Physiol. 1705 ~1714
90. Morales-Ruiz T, Ortega-Galisteo AP, Ponferrada-Marin MI, Martínez- Macías MI, Ariza RR, Roldán-Arjona T. DEMETER and REPRESSOR OF SILENCING 1 encode 5-methylcytosine DNA glycosylases. Natl Acad Sci USA, 2006, 103: 6853~6858
91. Manfred K, Manorama C J, Crowell N D. Rapid induction of genetic de -methylation and T- DNA gene expression in plant cells by 5-azacyosine derivations. Plant Molecular Biology, 1989, 12:413~423
92. Mirkovitch J, Mirault ME and Laemmli UK. Organization of the higher -order chromatin loop: specific DNA attachment sites on nuclear scaff - old. Cell, 1984, 39:223~232
93. Mielke C, Kohwi Y, Bode J. Hierarachical binding of DNA fragments derived from scaffold-attached regions: correlation of properties in vitro and function in vivo. Biochemistry, 1990, 29:7475 ~7485
94. Mankin S L, Allen G C, Phelan T, et al. Elevation of transgene express- ion level by flanking matrix attachment regions (MAR) is promoter de -pendent: a study of the interactions of six promoters with the RB7 3′MAR. Transgenic Res, 2003, 12:3~12
95. Morisawa G, Han-Yama A, Moda I, Tamai A, Iwabuchi M, Meshi T. AHM1, a novel type of nuclear matrix-localized, MAR binding protein with a single AT hook and a J domain-homologous region. Plant Cell, 2000, 12:1903~1916
96. Nakano Y, Steward N, Sekine M, Kusano T, Sano H. A tobacoo Nt - MET1 cDNA encoding a DNA methylthansferase: molecular character-ization and abnormal phenotype of transgene tobacoo plants. Drosop -hila melanogaster. Mol Cell Biol 18:2382~2391
97. Nieto-Sotelo J, Ichida A, Quail PH. PF1: An A-T hook containing DNA binding protein from rice that interacts with a functionally defined d(AT)-rich element in the oat phytochrome A3 gene promoter. Plant Cell, 1994, 6:287~301
98. Nakagomi K, Kohwi Y, Dickinson LA and Kohwi-Shigematsu T. A novel DNAbinding motif in the nuclear matrix attachment DNA-binding protein SATB1. Plant Cell Physiol, 2000, 41: 448~457
99. Namciu SJ, Blochlinger KB, Fournier RE. Human matrix attachment regions insulate transgene expression from chromosomal position effects in Mol Cell Biol, 1998, 14:1852~1860
100.Nan X, Hg H. H, Johnson C. A, Laherty C. D, Turner B. M, Eisenman RN, and Bird A, 1998, Transcriptional repression by the methyl-CpG- binding protein MeCP2 involves a histone deacetylase complex, Nature, 393:386~389
101.Onishi Y, Hanai S, Ohno T, Hara Y, Ishida N. Rhythmic SAF-A binding underlies circadian transcription of the Bmal1 gene. Mol Cell Biol, 2008, 28:3477~3488
102.Obrdlik A, Kukalev A, Louvet E, Ostlund Farrants AK, Caputo L, Percipalle P. The histone acetyl transferase PCAF associates with actin and hnRNP U for RNA polymerase II transcription. Mol Cell Biol, 2008, 28:6342~6357
103.Papa CM, Springer NM, Muszynski MG, Meeley R, Kaeppler SM. Maize chromomethylase Zea methyltransferase2 is required for CpNpG methylation. Plant Cell, 2001, 13(8): 1919~1928
104.Pienta KJ, Getzenberg RH, Coffey DS. Cell structure and DNA organization. Crit Rev Eukaryotic Gene Expression, 1991, 1:355~385
105.Richards EJ. DNA methylation and plant development. Trens genet 1997, 13: 319~322
106.Reeves R and Nissen M. S. Interaction of high mobility group-I (Y) nonhistone proteins with nucleosome core particles. J. Biol. Chem, 1990, 268:21137~21146
107.Romig H, Fackelmayer F O, Renz A et al. Characterization of SAF-A, a novel nuclear DNA binding protein from Hela cells with high affinity for nuclear matrix/scaffold attachment DNA elements. EMBO J, 1992, 11:3431~3440
108.Romig H, Ruff J, Fackelmayer F O et al. Characterisation of two in -tronic nuclear-matrix-attachment regions in the human DNA topoi -someraseI gene. Eur. J. Biochem, 1994, 221:411~419
109.Romig H, Ruff J, Fackelmayer FO, Patil MS, and Richter A. Charac -terisation of two intronic nuclear-matrix-attachment regions in the hu -man DNA topoisomerase I gene. Eur J Biochem, 1994, 221: 411~4
110.Renz A, Fackelmayer F O. Purification and molecular cloning of the scaffold attachment factor B (SAF-B), a novel human nuclear protein th -at specifically binds S/MARs-DNA. Nucl. Acids. Res. 1996, 24: 843~ 849
111.Saze H, Scheid OM, Paszkowski J. Maintenance of CpG methylation is essential for epigenetic inheritance during plant gametogenesis. Nature Genet, 2003, 34: 65~69
112.Soppe WJ, Jacobsen SE, Alonso-Blanco C, Jackson JP, Kakutani T, Koornneef M, Peeters AJ. The late flowering phenotype of fwa mutants is caused by gain-of-function epigenetic alleles of a homeodomain gene. Mol Cell, 2000, 6: 791~802
113.Steward N, Kusano T, Sano H. Expression of ZmMET1, a gene en -coding a DNA methyltransferase from maize, is associated not only with DNA replication in actively proliferating cells but also with altered DNA methylation status in cold-stressed quiescent cells. Nucleic Acid Res, 2000, 28: 3250~3259
114.Suoniemi A, Narvanto A and Schulman A H. The BARE-1 retro transposon is transcribed in barley from an LTR promoter active in transient assays. Plant Mol Biol, 1996, 31:295~306
115.Soppe W J, Jacobsen S E, Alonso-Blanco C, et al. The late flowering phenotype of fwa mutants is caused by gain-of-function epigenetic all -eles of a homeodomain gene. Mol Cell, 2000, 6:791-802
116.Skulachev MV, Ivanov PA, Karpova OV, Korpela T, Rodionova NP, Dorokhov YL, Atabekov JG. Internal initiation of translation directed by the 5'-untranslated region of the tobamovirus subgenomic RNA I. Virology. 1999, 263: 139~154
117.Schwechheimer C, Smith C, Bevan M W. The activities of acidic and glutamine - rich transcriptional activation domains in plants cells: desi -gn of modular transcription factors for high - level expression.Plant Molecular Biology, 1998, 36: 195~204
118.Sander M and Hsieh T S. Drosophila topoisomeraseⅡdouble-strand DNA cleavage: analysis of DNA sequence homology at the cleavage site. Nucl. Acids Res, 1985, 13:1057~1072
119.Sidorenko L, Bruce W, Maddock S, Tagliani L, Li X, Daniels M, Pe -terson T. (2003) Functional analysis of two matrix attachment region (MAR) elements in transgenic maize plants. Transgenic Res 12:137~ 154
120.Sundaresan V, Springer P, Volpe T, et al. Patterns of geneaction in pl -ant development revealed by enhancer trap and gene trap transposable elements. Gene Dev. 1995, 9: 1797~1810
121.Samaniego R, de la Torre C, Moreno Díaz de la Espina S. Charac -terization, expression and subcellular distribution of a novel MFP1 (matrix attachment region-binding filament-like protein1) in onion. Protoplasma, 2008, 233:31~38
122.Samaniego R, Jeong SY, de la Torre C, Meier I, Moreno Díaz de la Espina S. CK2 phosphorylation weakens 90 kDa MFP1 association to the nuclear matrix in Allium cepa. J Exp Bot, 2006, 57:113~24
123.Thomas JO, Travers AA. HMG1 and 2, and related architectural DNA-binding proteins. Trends Biochem Sci, 2001, 26:167~174
124.Thompson, E. M, Christians, E, Stinnakre, M. G. and Renard, J. P. Scaffold attachment regions stimulate HSP70. 1 expression in mouse preimplantation embryos but not in differentiated tissues. Mol. Cell. Biol. 1994, 14, 4694~4703.
125.Thompson, E. M, Legouy, E, Christians, E. and Renard, J. P. Pro -gressive maturation of chromatin structure regulates HSP70. 1 gene ex -pression in the preimplentation mouse embryo. Development, 1995, 121, 3425 ~ 3437.
126.Tsutsui K, Okada S, Watarai S, Seki S, Yasuda T, Shohmori T. Iden -tification and charaterization of a nuclear scaffold protein that bids the matrix attachment region DNA. J Biol Chem, 1993, 268: 12886 ~12894
127.Van der Geest AH, Hall GE Jr, Spiker S and Hall TC. Theβ-phaseolin gene is flanked by matrix attachment regions. Plant J, 1994, 6:413-423
128.Von Kries J P, Buhrmester H, Stratling W H. A matrix/scaffold att -achment region binding protein-identification, purification and mode of binding. Cell, 1991, 64: 123~135
129.Wassenegger M. RNA-directed DNAmethylation. Plant Mol Biol, 2000, 43:203~ 220
130.Weiler K S, Wakimoto B T. Heterochromatin and gene expression in Drosophila. Annu. Rev. Genet. 1995, 29: 577~605
131.Webster CI, Cooper MA, Packman LC, Williams DH, Gray JC. Kinetic analysis of high-mobility-group proteins HMG-1 and HMG-I/Y binding to cholesterol-tagged DNA on a supported lipid monolayer. Nucleic Acids Res, 2000, 28:1618~1624
132.Webster CI, Packman LC, Gray JC. HMG-1 enhances HMG-I/Y binding to an A/T-rich enhancer element from the pea plastocyanin gene. Eur J Biochem, 2001, 268:3154~3162
133.Wu M, and Ho S. M, 2004, PMP24, a gene identified by MSRF, undergoes DNA hypermethylation-associated gene silencing during cancer progression in an LNCaP model, Oncogene, 23:250~259
134.Wolffe A P, Matzke M A. Epigenetics: regulation through repression. Science, 1999, 286: 481~486
135.Wolffe A P. Transcription control: Repressed repeats express them selves. Curr. Biol. 1997, 7: R796~R798
136.Xiao W, Custard KD, Brown RC, Lemmon BE, Harada JJ, Goldberg RB. Fischer RL. DNA methylation is critical for Arabidopsis embryog enesis and seed viability. Plant Cell, 2006, 18: 805~814
137.Xiao W, Gehring M, Choi Y, Margossian L, Pu H, Harada J, Goldberg R, Pennell R, Fischer R. Imprinting of the MEA Polycomb gene is controlled by antagonism between MET1 methyltransferase and DME glycosylase. Dev Cell, 2003, 5: 891~901
138.Yamasaki K, Akiba T, Yamasaki T and Harata K. Structural basis for recognition of the matrix attachment region of DNA by transcription factor SATB1. Nucleic Acids Res, 2007, 35: 5073~5084
139.Zilberman D, Cao X, Johansen LK, Xie Z, Carrington JC, Jacobsen SE. Role of Arabidopsis ARGONAUTE4 in RNA-directed DNA meth ylation triggered by inverted repeats. Curr Biol, 2004
140.Zemach A, Li Y, Wayburn B, Ben-Meir H, Kiss V, Avivi Y, Kalchenko V, Jacobsen SE, Grafi G. DDM1 binds Arabidopsis Methyl-CpG binding domain proteins and affects their subnuclear localization. Plant Cell, 2005, 17: 1549~1558
141.Zilberman D, Cao X, Johansen LK, Xie Z, Carrington JC, Jacobsen SE. Role of Arabidopsis ARGONAUTE4 in RNA-directed DNA meth yllation triggered by inverted repeats. Curr Biol, 2004, 14, 1214~1220
142.Zheng X, Pontes O, Zhu J, Miki D, Zhang F, Li WX, Iida K, Kapoor A, Pikaard CS, Zhu JK: ROS3 is anRNA-binding protein required for DNA demethylation in Arabidopsis. Nature 2008
143.Zhao K, K?s E, Gonzalez E et al. SARdependent mobilization of his -tone H1 by HMG-I/Y in vitro:HMG-I/Y is enriched in H1~depleted chromatin. EMBO J. 1993, 12:3237~3247
144.Zhang W, Wu Q, Pwee KH, Jois SDS, Kini RM. Characterization of the interaction of wheat HMGa with linear and four-way junction DNA Biochemistry, 2003a, 42:6596~6607
145.Zhang W, Wu Q, Pwee KH, Kini RM. Interaction of wheat high- mobility -group proteins with four-way-junction DNA and characteriz ation of the structure and expression of HMGA gene. Arch Biochem Biophys, 2003b, 409:357~366
146.Zhao K, Kas E, Gonzalez E, Laemmli UK. SAR-dependent mobiliz -ation of histone H1 by HMG-I/Y in vitro: HMG-I/Y is enriched in H1 -depleted chromatin. EMBO J, 1993, 12: 3237~3247
2.张可伟,王健美,杨国栋,郭兴启,温孚江,崔德才,郑成超。强MAR的分离及其体内外功能鉴定。科学通报,2002,47:1527~1577.
3. Aenisch R, Bird A. Epigenetic regulation of gene expression: how the genome integrates intrinsic and environmential signals. Nat Genet, 2003, 33:245~254
4. Aufsatz W, Mette MF, Winden J, Matzke AJM, Matzke M. RNA directed DNA methylation in Arabidopsis. Proc Natl Acad Sci USA, 2002, 16(Suppl.)4: 499~506
5. Allen GC, Hall G Jr, Michalowski S, Newman W, Spiker S, Weissinger AK, Thompson WF. High-level transgene expression in plant cells: effects of a strong scaffold attachment region from tobacco. Plant Cell, 1996, 8:899~913
6. Allen G A, Hall G E Jr, Childs L C. Scaffold-attached regions increase reporter gene expression in stably transformed plant cells. Plant Cell, 1993, 5:603~613
7. Allen G C, Hall G E Jr, Michalowski S et al. High-level transgene expression in plant cells; effect of a strong scaffold attachment region from tabacoo. Plant Cell, 1996, 8:899~913
8. Antes TJ, Namicu SJ, Fournier RE and Levy-Wilson B. The 5′- boundary of the human apolipoprotein B chromatin domain in intestinal cells. Biochemistry, 2001, 40:6731~6742
9. Anandalakshmi R, Pruss G J, Ge X et al. A viral suppressor of genesilencing in plants. Proc. Natl. Acad. Sci. USA, 1998, 95: 13079 ~13084.
10. Allen GC, Spiker S, Thompson W F. Use of matrix attachment regions (MARs) to minimize transgene silencing. Plant Mol Biol, 2000, 43: 361~376
11. Adachi Y, Kas E, Laemmli UK. Preferential, cooperative binding of DNA topoisomerase II to scaffold-associated regions. EMBO J, 1989, 8:3997~4006
12. Alvarez J D, Yasui DH, Niida H, Joh T, Loh DY, and Kohwi- Shigematsu T. The MAR-binding protein SATB1 orchestrates temporal and spatial expression of multiple genes during T-cell development. Genes & Dev, 2000, 14: 521~535
13. Baroux C, Spillane C, Grossniklaus U. Genomic imprinting during seed development. Adv Genet Academic Press San Diego USA, 2002: 165 ~214.
14. Bender J. DNA methylation and epigenetics. Annu Rev Plant Biol, 2004, 55: 41~68
15. Bestor TH. The DNA methyltransferases of mammals. Hum Mol Genet, 2000, 9: 2395~2402
16. Bartee L, Malagnac F, Bender J. Arabidopsis cmt3 chromomethylase mutations block non-CG methylation and silencing of an endogenous gene. Genes Dev, 2001, 15: 1753~1758.
17. Brzeski J, Jerzmanowski A. Deficient in DNA methylation 1 (DDM1) defines a novel family of chromatin remodling factors. J Biol Chem, 2003, 278: 823~828.
18. Bartee L, Bender J. Two Arabidopsis methylation- deficiency mutations confer only partial effects on a methylated endogenous gene family. Nucleic Acids Res, 2001, 29: 2127~2134
19. Burn J E, Bagnall D J, Metzger J D, et al. DNA methylation, vernalization, and the initiation of flowering. Proc Natl Acad Sci USA, 1993, 90:287~ 291.
20. Buryanov YI, Shevchuk TV. DNA methyltransferases and structural-functional specificity of eukaryotic DNA modification. Biochemistry (Moscow), 2005, 70:730~742
21. Berezney R and Coffey DS. Identification of a nuclear protein matrix. Biochem Biophys Res Commun, 1974, 60:1410~1470
22. Breyne P, Van Montagu M, Depicker A, et al. Characterization of a plant scaffold attachment region in a DNA fragment that normalizes transgene expression in tobacco. Plant Cell, 1992, 4:463~471.
23. Bode J, Kohwi Y, Dickinson L et al. Biological significance of unwinding capabiliyu of nuclear matrix-associating DNAs. Science, 1992, 255:195~197
24. Breyne P, Van Montagu M, Gheysen G. The role of scaffold attachment region in the structural and functional organization of plant chromatin. Transgenic Res, 1994, 3:195~202.
25. Benham C, Kohwi-Shigematsu T, Bode J. Stressinducedduplex DNA destabilization in scaffold/matrix attachment regions. J. Mol. Biol. 1997, 274:181~196
26. Brouwer C, Bruce W, Maddock S, et al. Suppression of transgnene silencing by matrix attachment regions in maize: a dual role for the maize 5′ADH1 matrix attachment region. Plant cell, 2002, 14:2251 ~2264
27. Brigneti G, Voinnet O, Li W X, et al. Viral pathogenicity deterants are suppressors of transgene silencing in Nicotiana benthamiana. EMBO J. 1998, 17: 6739~6746
28. Belshaw NJ, Hakola S, Nevalanien, Penttil? M, Suominen P, Archer DB. Trichoderma reesei sequences that bind to the nuclear matrix enhance transformation frequency. Mol. Gen. Genet, 1997, 256: 18~27
29. Berezney R and Coffey DS. Identification of a nuclear protein matrix. Biochem Biophys Res Commun, 1974, 60:1410~1470
30. Bianchi ME, Agresti A. HMG proteins: Dynamic players in gene regulation and differentiation. Curr Opin Genet Dev, 2005, 15: 496~506
31. Bird A, 2002, DNA methylation patterns and epigenetic memory, Genes Dec. 16:6~21
32. Cao X, Springer NM, Muszynski MG, Phillips RL, Kaeppler S, Jacobsen SE. Conserved plant genes with similarity to mammalian de novo DNA methyltransferases. Proc Natl Acad Sci USA, 2000 97: 4979~4984.
33. Cao X, Jacobsen SE. Role of the Arabidopsis DRM methyltransferases in de novo DNA methylation and gene silencing. Curr Biol, 2002, 12: 1138~1144.
34. Chan SW, Zilberman D, Xie Z, Johansen LK, Carrington JC, Jacobsen SE. RNA silencing genes control de novo DNA methylation. Science, 2004, 303:1336
35. Cao X, Aufsatz W, Zilberman D, Mette MF, Huang MS, Matzke M, Jacobsen SE. Role of the DRM and CMT3 methyltransferases in RNA-directed DNA methylation. Curr Biol, 2003, 13: 2212~2217.
36. Curradi M, Izzo A, Badaracco G, et al. Molecular Mechanisms of Gene Silencing Mediated by DNA Methylation. Mol Cell Biol, 2002, 22:3157~3173
37. Chan SW, Henderson IR, Jacobsen SE. Gardening the genome: DNA methylation in Arabidopsis thaliana. Nature Publishing Group, 2005, 6:351~360.
38. Chan SW, Zilberman D, Xie Z, Johansen LK, Carringtion JC, Jacobsen SE. RNA silencing genes control de novo DNA methylation. Science, 2004, 303:1336~1336.
39. Cogon C, Macimo G. Gene silencing in Macrospore crassa requires a protein homologous to RNA-dependent RNA polymerase. Nature, 1999, 399:166~168.
40. Chinnusamy V, Ohta M, Kanrar S, Lee BH, Hong X, Agarwal M, Zhu JK. ICE1: a regulator of cold-induced transcriptome and freezing tolerance in Arabidopsis Genes Dev. 2003, 17: 1043~1054.
41. Cockerill PN, Garrard WT. Chromosomal loop anchorage of the kappa immunoglobulin gene occurs next to the enhancer in a region containing topoisomeraseⅡsites. Cell, 1986, 44:273~282.
42. Cornelis M. Van Drunen, Oosterling R W, Keultjes G M et al. Analysis of the chromatin domain organization around the plastocyanin gene reveals an MARs-specific sequence element in Arabidopsis thalami. Nucleic Acids Research, 1997, 25:3904~3911
43. Dijlwell PA, Hamlin JL. Matrix attachment regions are positioned near replication initiation sites, gene, and an interam plicon junction in the amplified dihydrofolate reductase domain of Chinese hamster ovary cell. Mol Cell Biol, 1988, 8:5398~5409.
44. Dietz A, Kay V, Schlacker T, Landsmann J and Bode J. A plant scaffold attached region detected close to a T-DNA integration site is active in mammalian cells. Nucleic Acids Res, 1994, 22: 2744~2751
45. Dickinson LA, Kohwi-Shigematsu T. Nucleolin is a matrix attachment region DNA-binding protein that specifically recognizes a region with high base-unpairing potential. Mol Cell Biol, 1995, 15: 456~465
46. Dobreva G, Dambacher J, Grosschedl R. SUMO modification of a novel MAR-binding protein, SATB2, modulates immunoglobulin mu gene expression. Genes Dev, 2003, 17:3048~ 3061
47. Eads CA, Danenberg KD, Kawakami K, Saltz LB, Blake C, Shibata D, Danenberg PV, Elmavan T, Proux F, Vaucheret H. Arabidopsis RPA2: a genetic link among transcriptional gene silencing, DNA repair, and DNA replication. Curr Biol, 2005, 15: 1919~1925
48. Finnegan E J, Genger R K, Kovac K, et al. DNA methylation and the promotion of flowering by vernalization. Proc Naitl Acad Sci USA, 1998, 95:5824~ 5829
49. Fagard M, Vaucheret H. (Trans) Gene silencing in plants: how many mechanisms? Annu Rev Plant Physiol Plant Mol Biol, 2000, 51: 167~ 194
50. Fujiwara S, Matsuda N, Sato T, et al. Molecular properties of a matrix attachment region~binding protein located in the nucleoli of tobacco cells. Plant Cell Physiol, 2002, 43:1558~1567
51. Fackelmayer F O, Dahm K, Renz A et al. Nucleic-acid-binding property -es of hnRNP-U/SAF-A, a nuclear-matrix protein which binds DNA and RNA in vivo and in vitro. Eur. J. Biochem. 1994, 211: 747~ 757
52. Fackelmayer F O and Richter A. Purification of two isoforms of hnRNP -U and characterization of their nucleic acid binding activity. Biochemis -try, 1994, 33:10416~10422
53. Fackelmayer FO, Dahm K, Renz A, Ramsperger U, Richter A. Nucleic -acid-binding properties of hnRNP-U/SAF-A, a nuclear -matrix protein which binds DNA and RNA in vivo and in vitro. Eur J Biochem, 1994, 221:749~7
54. Fujimoto S, Matsunaga S, Yonemura M, Uchiyama S, Azuma T, Fukui K. Identification of a novel plant MAR DNA binding protein localized on chromosomal surfaces. Plant Mol Biol, 2004, 56:225~239
55. Gruenbaum Y, Naveh MT, Cedar H, Razin A. Sequence specificity of methylation in higher plant DNA. Nature, 1981, 292: 860~862
56. Gheysen G, Montagu M V and Zambryski P. Integration of Agrobact- erium tumefaciens transfer DNA (T-DNA) involves rearrangements of target plant DNA sequences. Proc. Natl Acad. Sci. USA, 1987, 84: 6169 ~6173
57. Gasser S M, Laemmli U K. The organization of chromatin loops: characterization of scaffold attachment sites. EMBO, 1986, 5:511~518
58. Gohring F and Fackelmayer. The scaffold/matrix attachment region binding protein hnRNP-U (SAF-A) is directly bound to chromosomalDNA in vivo: a chemical cross-linking study. Biochemistry, 1997, 36: 8276~8283
59. Grasser KD, Launholt D. Chromatin-associated architectural HMGA and HMGB proteins assist transcription factor function. In Regulation of Transcription in Plants, K. D. Grasser, ed. (Oxford, UK: Blackwell Publishing) Plant Physiol, 2006, 54~78
60. Henikoff S, Comai L. A DNA methyltransferase homolog with a chrom -odomain exists in multiple polymorphic forms in Arabidopsis. Genetic -s, 1998, 149: 307~318.
61. Hall G E, Jr, Allen G C, et al. Nuclear scaffolds and scaffold–attachme -nt regions in higher plants. Proc. Natl. Acad. Sci. USA, 1991. 88: 9320 ~9324.
62. Holmes-Davis R, Comai L. The matrix attachment regions (MARs) associated with the Heat Shock Cognate 80 gene (HSC80) of tomato represent specific regulatory elements. Mol Genet Genomics, 2002, 266:891~898
63. Hua Xue, Yu-TaoYang, Chang-AiWu, Guo-Dong Yang, Cheng-Chao Zheng. TM2, a novel strong matrix attachment region isolated from tobacco, increases transgene expression in transgenic rice calli and plants, Theor. Appl. Genet. 2005, 110: 620~627
64. Izaurralde E, Kas E, Laemmli UK. Highly preferential nude H1 assemb -ly on sacffold-associated regions. J Mol Biol, 1989, 210: 573~585
65. Jacobsen SE, Meyerowitz EM. Hypermethylated SUPERMAN epigene -tic alleles in Arabidopsis. Science, 1997, 277: 1100~1103
66. Johns EW. The HMG Chromosomal Proteins. Academic Press, 1982, London
67. Jeong SY, Peffer N, Meier I. Phosphorylation by protein kinase CKII modulates the DNA-binding activity of a chloroplast nucleoid-associate -ed protein. Planta, 2004, 219:298~302
68. Jackson D A. Chromatin domains and nuclear compartments: establish -ing sites of gene expression in eukaryotic nuclei. Mol Biol Rep 1997, 24: 209~220
69. Jackson D A, Dickinson P and Cook P R. Attachment of DNA to the nucleoskeleton of HeLa cells examined using physiological conditions. Nucl. Acids Res. 1990a. 18: 4385~4393
70. Kass SU, Pruss D, Wolffe AP, et al. How does DNAmethylation repress transcription? Trens genet, 1997, 13:444~449
71. Klose R J, Bird A P. Genomic DNA methylation:the mark and its media -tors. Trends Biochem Sci, 2006, 31:89~ 97
72. Kozak M. Point mutations define a sequence flanking the AUG initiator codon that modulates translation by eukaryotic ribosomes. Cell, 1986, 44: 283~292
73. Kas E, Lzaurralde E K, Laemmli U K. Highly preferential nucleation of histone H1 assembly on scaffold-associated regions. Mol. Biol. 1989, 210:587~599
74. Kas E, Lzaurralde E K, Laemmli U K. Specific inhibition of DNA binding to nuclear scaffolds and histone H1 by distamycin. Mol. Biol. 1989, 210:573~585
75. Kas E and Chasin L A. Anchorage of the Chinese hamster dihydrofolate reductase gene to the nuclear scaffold occurs in an intragenic region. Mol. Biol, 1987, 198:677~692
76. Kas E, Plojak L, Adachi Y et al. A model for chromatin opening: stimulation of topoisomeraseⅡand restriction enzyme cleavage of chromatin by histaminic. EMBO, 1993, 12:115~126
77. Kipp MF, Gohriong T, Ostendorp CM. SAF-Box, a conserved protein domain that specifically recognizes scaffold attachment region DNA. Mol. Cell. Biol. 2000, 20:7480~7489
78. Kohwi-Shigematsu T, Maass K, and Bode J. (1997) Athymocyte factor SATB1 suppresses transcription of stably integrated matrix - attachment region-linked reporter genes. Biochemistry 36: 12005 ~12010
79. Kiledjian M, and Dreyfuss G. Primary structure and binding activity of the hnRNP U protein: binding RNA through RGG box. EMBO J, 1992, 11:2655~2664
80. Kipp M, Gohring F, Ostendorp T, van Drunen CM, van Driel R, Przybylski M, Fackelmayer FO. SAF-Box, a conserved protein domain that specifically recognizes scaffold attachment region DNA. Mol Cell Biol, 2000, 20:7480~7489
81. Lindroth AM, Cao X, Jackson JP, Zilberman D, McCallum CM, Heniko -ff S, Jacobsen SE. Requirement of CHROMOMETHYLASE3 for main -tenance of CpXpG methylation. Science, 2001, 292: 2077~2080
82. Lichtenstein M, Bergmany C H. B-cell-specific demethylation: A novel role for the intronic chain enhance sequence. Cell, 1994, 1: 913~923
83. Lzaurralde E, Mirkovitch J, Laemmli UK. Interaction of DNA with nuclear scaffolds in vitro. J Mol. Biol, 1988, 200:111~125
84. Ludérus M E, den Blaauwen J L, Smit O J B et al. Binding of matrix attachment regions to lamin polymers involves single-stranded regions and the minor groove. Mol. Cell. Biol. 1994, 14:6297~6305
85. Ludérus M E, A de Graaf, Mattia E et al. Binding of matrix attachment regions to lamin B1. Cell, 1992, 70:949~959
86. Liu WM, Guerra-Vladusic FK, Kurakata S, Lupu R, Kohwi-Shigematsu T. HMG-I(Y) recognizes base-unpairing regions of matrix attachment sequences and its increased expression is directly linked to metastatic breast cancer phenotype. Cancer Res, 1999, 59: 5695~ 5703
87. Levine, A, A. Yeivin, E. Ben Asher, Y. Aloni, and A. Razin. 1993. His -tone H1-mediated inhibition of transcription initiation of methylated te -mplates in vitro. J. Biol. Chem. 268:21754~21759.
88. Malagnac F, Bartee L, Bender J. An Arabidopsis SET domain protein required for maintenance but not estab lishment of DNA methylation. EMBO J, 2002, 21: 6842~6852
89. Michael McArthur and Jean O. Thomas, A preference of histone Hi for methylated DNA, 1996, The EMBO Journal vol. 15 no. 7 Plant Physiol. 1705 ~1714
90. Morales-Ruiz T, Ortega-Galisteo AP, Ponferrada-Marin MI, Martínez- Macías MI, Ariza RR, Roldán-Arjona T. DEMETER and REPRESSOR OF SILENCING 1 encode 5-methylcytosine DNA glycosylases. Natl Acad Sci USA, 2006, 103: 6853~6858
91. Manfred K, Manorama C J, Crowell N D. Rapid induction of genetic de -methylation and T- DNA gene expression in plant cells by 5-azacyosine derivations. Plant Molecular Biology, 1989, 12:413~423
92. Mirkovitch J, Mirault ME and Laemmli UK. Organization of the higher -order chromatin loop: specific DNA attachment sites on nuclear scaff - old. Cell, 1984, 39:223~232
93. Mielke C, Kohwi Y, Bode J. Hierarachical binding of DNA fragments derived from scaffold-attached regions: correlation of properties in vitro and function in vivo. Biochemistry, 1990, 29:7475 ~7485
94. Mankin S L, Allen G C, Phelan T, et al. Elevation of transgene express- ion level by flanking matrix attachment regions (MAR) is promoter de -pendent: a study of the interactions of six promoters with the RB7 3′MAR. Transgenic Res, 2003, 12:3~12
95. Morisawa G, Han-Yama A, Moda I, Tamai A, Iwabuchi M, Meshi T. AHM1, a novel type of nuclear matrix-localized, MAR binding protein with a single AT hook and a J domain-homologous region. Plant Cell, 2000, 12:1903~1916
96. Nakano Y, Steward N, Sekine M, Kusano T, Sano H. A tobacoo Nt - MET1 cDNA encoding a DNA methylthansferase: molecular character-ization and abnormal phenotype of transgene tobacoo plants. Drosop -hila melanogaster. Mol Cell Biol 18:2382~2391
97. Nieto-Sotelo J, Ichida A, Quail PH. PF1: An A-T hook containing DNA binding protein from rice that interacts with a functionally defined d(AT)-rich element in the oat phytochrome A3 gene promoter. Plant Cell, 1994, 6:287~301
98. Nakagomi K, Kohwi Y, Dickinson LA and Kohwi-Shigematsu T. A novel DNAbinding motif in the nuclear matrix attachment DNA-binding protein SATB1. Plant Cell Physiol, 2000, 41: 448~457
99. Namciu SJ, Blochlinger KB, Fournier RE. Human matrix attachment regions insulate transgene expression from chromosomal position effects in Mol Cell Biol, 1998, 14:1852~1860
100.Nan X, Hg H. H, Johnson C. A, Laherty C. D, Turner B. M, Eisenman RN, and Bird A, 1998, Transcriptional repression by the methyl-CpG- binding protein MeCP2 involves a histone deacetylase complex, Nature, 393:386~389
101.Onishi Y, Hanai S, Ohno T, Hara Y, Ishida N. Rhythmic SAF-A binding underlies circadian transcription of the Bmal1 gene. Mol Cell Biol, 2008, 28:3477~3488
102.Obrdlik A, Kukalev A, Louvet E, Ostlund Farrants AK, Caputo L, Percipalle P. The histone acetyl transferase PCAF associates with actin and hnRNP U for RNA polymerase II transcription. Mol Cell Biol, 2008, 28:6342~6357
103.Papa CM, Springer NM, Muszynski MG, Meeley R, Kaeppler SM. Maize chromomethylase Zea methyltransferase2 is required for CpNpG methylation. Plant Cell, 2001, 13(8): 1919~1928
104.Pienta KJ, Getzenberg RH, Coffey DS. Cell structure and DNA organization. Crit Rev Eukaryotic Gene Expression, 1991, 1:355~385
105.Richards EJ. DNA methylation and plant development. Trens genet 1997, 13: 319~322
106.Reeves R and Nissen M. S. Interaction of high mobility group-I (Y) nonhistone proteins with nucleosome core particles. J. Biol. Chem, 1990, 268:21137~21146
107.Romig H, Fackelmayer F O, Renz A et al. Characterization of SAF-A, a novel nuclear DNA binding protein from Hela cells with high affinity for nuclear matrix/scaffold attachment DNA elements. EMBO J, 1992, 11:3431~3440
108.Romig H, Ruff J, Fackelmayer F O et al. Characterisation of two in -tronic nuclear-matrix-attachment regions in the human DNA topoi -someraseI gene. Eur. J. Biochem, 1994, 221:411~419
109.Romig H, Ruff J, Fackelmayer FO, Patil MS, and Richter A. Charac -terisation of two intronic nuclear-matrix-attachment regions in the hu -man DNA topoisomerase I gene. Eur J Biochem, 1994, 221: 411~4
110.Renz A, Fackelmayer F O. Purification and molecular cloning of the scaffold attachment factor B (SAF-B), a novel human nuclear protein th -at specifically binds S/MARs-DNA. Nucl. Acids. Res. 1996, 24: 843~ 849
111.Saze H, Scheid OM, Paszkowski J. Maintenance of CpG methylation is essential for epigenetic inheritance during plant gametogenesis. Nature Genet, 2003, 34: 65~69
112.Soppe WJ, Jacobsen SE, Alonso-Blanco C, Jackson JP, Kakutani T, Koornneef M, Peeters AJ. The late flowering phenotype of fwa mutants is caused by gain-of-function epigenetic alleles of a homeodomain gene. Mol Cell, 2000, 6: 791~802
113.Steward N, Kusano T, Sano H. Expression of ZmMET1, a gene en -coding a DNA methyltransferase from maize, is associated not only with DNA replication in actively proliferating cells but also with altered DNA methylation status in cold-stressed quiescent cells. Nucleic Acid Res, 2000, 28: 3250~3259
114.Suoniemi A, Narvanto A and Schulman A H. The BARE-1 retro transposon is transcribed in barley from an LTR promoter active in transient assays. Plant Mol Biol, 1996, 31:295~306
115.Soppe W J, Jacobsen S E, Alonso-Blanco C, et al. The late flowering phenotype of fwa mutants is caused by gain-of-function epigenetic all -eles of a homeodomain gene. Mol Cell, 2000, 6:791-802
116.Skulachev MV, Ivanov PA, Karpova OV, Korpela T, Rodionova NP, Dorokhov YL, Atabekov JG. Internal initiation of translation directed by the 5'-untranslated region of the tobamovirus subgenomic RNA I. Virology. 1999, 263: 139~154
117.Schwechheimer C, Smith C, Bevan M W. The activities of acidic and glutamine - rich transcriptional activation domains in plants cells: desi -gn of modular transcription factors for high - level expression.Plant Molecular Biology, 1998, 36: 195~204
118.Sander M and Hsieh T S. Drosophila topoisomeraseⅡdouble-strand DNA cleavage: analysis of DNA sequence homology at the cleavage site. Nucl. Acids Res, 1985, 13:1057~1072
119.Sidorenko L, Bruce W, Maddock S, Tagliani L, Li X, Daniels M, Pe -terson T. (2003) Functional analysis of two matrix attachment region (MAR) elements in transgenic maize plants. Transgenic Res 12:137~ 154
120.Sundaresan V, Springer P, Volpe T, et al. Patterns of geneaction in pl -ant development revealed by enhancer trap and gene trap transposable elements. Gene Dev. 1995, 9: 1797~1810
121.Samaniego R, de la Torre C, Moreno Díaz de la Espina S. Charac -terization, expression and subcellular distribution of a novel MFP1 (matrix attachment region-binding filament-like protein1) in onion. Protoplasma, 2008, 233:31~38
122.Samaniego R, Jeong SY, de la Torre C, Meier I, Moreno Díaz de la Espina S. CK2 phosphorylation weakens 90 kDa MFP1 association to the nuclear matrix in Allium cepa. J Exp Bot, 2006, 57:113~24
123.Thomas JO, Travers AA. HMG1 and 2, and related architectural DNA-binding proteins. Trends Biochem Sci, 2001, 26:167~174
124.Thompson, E. M, Christians, E, Stinnakre, M. G. and Renard, J. P. Scaffold attachment regions stimulate HSP70. 1 expression in mouse preimplantation embryos but not in differentiated tissues. Mol. Cell. Biol. 1994, 14, 4694~4703.
125.Thompson, E. M, Legouy, E, Christians, E. and Renard, J. P. Pro -gressive maturation of chromatin structure regulates HSP70. 1 gene ex -pression in the preimplentation mouse embryo. Development, 1995, 121, 3425 ~ 3437.
126.Tsutsui K, Okada S, Watarai S, Seki S, Yasuda T, Shohmori T. Iden -tification and charaterization of a nuclear scaffold protein that bids the matrix attachment region DNA. J Biol Chem, 1993, 268: 12886 ~12894
127.Van der Geest AH, Hall GE Jr, Spiker S and Hall TC. Theβ-phaseolin gene is flanked by matrix attachment regions. Plant J, 1994, 6:413-423
128.Von Kries J P, Buhrmester H, Stratling W H. A matrix/scaffold att -achment region binding protein-identification, purification and mode of binding. Cell, 1991, 64: 123~135
129.Wassenegger M. RNA-directed DNAmethylation. Plant Mol Biol, 2000, 43:203~ 220
130.Weiler K S, Wakimoto B T. Heterochromatin and gene expression in Drosophila. Annu. Rev. Genet. 1995, 29: 577~605
131.Webster CI, Cooper MA, Packman LC, Williams DH, Gray JC. Kinetic analysis of high-mobility-group proteins HMG-1 and HMG-I/Y binding to cholesterol-tagged DNA on a supported lipid monolayer. Nucleic Acids Res, 2000, 28:1618~1624
132.Webster CI, Packman LC, Gray JC. HMG-1 enhances HMG-I/Y binding to an A/T-rich enhancer element from the pea plastocyanin gene. Eur J Biochem, 2001, 268:3154~3162
133.Wu M, and Ho S. M, 2004, PMP24, a gene identified by MSRF, undergoes DNA hypermethylation-associated gene silencing during cancer progression in an LNCaP model, Oncogene, 23:250~259
134.Wolffe A P, Matzke M A. Epigenetics: regulation through repression. Science, 1999, 286: 481~486
135.Wolffe A P. Transcription control: Repressed repeats express them selves. Curr. Biol. 1997, 7: R796~R798
136.Xiao W, Custard KD, Brown RC, Lemmon BE, Harada JJ, Goldberg RB. Fischer RL. DNA methylation is critical for Arabidopsis embryog enesis and seed viability. Plant Cell, 2006, 18: 805~814
137.Xiao W, Gehring M, Choi Y, Margossian L, Pu H, Harada J, Goldberg R, Pennell R, Fischer R. Imprinting of the MEA Polycomb gene is controlled by antagonism between MET1 methyltransferase and DME glycosylase. Dev Cell, 2003, 5: 891~901
138.Yamasaki K, Akiba T, Yamasaki T and Harata K. Structural basis for recognition of the matrix attachment region of DNA by transcription factor SATB1. Nucleic Acids Res, 2007, 35: 5073~5084
139.Zilberman D, Cao X, Johansen LK, Xie Z, Carrington JC, Jacobsen SE. Role of Arabidopsis ARGONAUTE4 in RNA-directed DNA meth ylation triggered by inverted repeats. Curr Biol, 2004
140.Zemach A, Li Y, Wayburn B, Ben-Meir H, Kiss V, Avivi Y, Kalchenko V, Jacobsen SE, Grafi G. DDM1 binds Arabidopsis Methyl-CpG binding domain proteins and affects their subnuclear localization. Plant Cell, 2005, 17: 1549~1558
141.Zilberman D, Cao X, Johansen LK, Xie Z, Carrington JC, Jacobsen SE. Role of Arabidopsis ARGONAUTE4 in RNA-directed DNA meth yllation triggered by inverted repeats. Curr Biol, 2004, 14, 1214~1220
142.Zheng X, Pontes O, Zhu J, Miki D, Zhang F, Li WX, Iida K, Kapoor A, Pikaard CS, Zhu JK: ROS3 is anRNA-binding protein required for DNA demethylation in Arabidopsis. Nature 2008
143.Zhao K, K?s E, Gonzalez E et al. SARdependent mobilization of his -tone H1 by HMG-I/Y in vitro:HMG-I/Y is enriched in H1~depleted chromatin. EMBO J. 1993, 12:3237~3247
144.Zhang W, Wu Q, Pwee KH, Jois SDS, Kini RM. Characterization of the interaction of wheat HMGa with linear and four-way junction DNA Biochemistry, 2003a, 42:6596~6607
145.Zhang W, Wu Q, Pwee KH, Kini RM. Interaction of wheat high- mobility -group proteins with four-way-junction DNA and characteriz ation of the structure and expression of HMGA gene. Arch Biochem Biophys, 2003b, 409:357~366
146.Zhao K, Kas E, Gonzalez E, Laemmli UK. SAR-dependent mobiliz -ation of histone H1 by HMG-I/Y in vitro: HMG-I/Y is enriched in H1 -depleted chromatin. EMBO J, 1993, 12: 3237~3247