跳到主要內容

臺灣博碩士論文加值系統

(3.236.110.106) 您好!臺灣時間:2021/07/24 06:29
字體大小: 字級放大   字級縮小   預設字形  
回查詢結果 :::

詳目顯示

: 
twitterline
研究生:蘇家興
研究生(外文):Chia-Hsin Su
論文名稱:p53基因轉錄在附基因體結構上的調控機制
論文名稱(外文):p53 chromatin epigenetic domain organization and p53 transcription
指導教授:徐明達徐明達引用關係
指導教授(外文):Ming-Ta Hsu
學位類別:博士
校院名稱:國立陽明大學
系所名稱:生化暨分子生物研究所
學門:生命科學學門
學類:生物化學學類
論文種類:學術論文
論文出版年:2009
畢業學年度:97
語文別:英文
論文頁數:123
中文關鍵詞:去氧核醣核酸甲基化染色質蛋白的修飾染色質體
外文關鍵詞:chromatin3c assayDNA methylationhistone modification
相關次數:
  • 被引用被引用:0
  • 點閱點閱:300
  • 評分評分:
  • 下載下載:33
  • 收藏至我的研究室書目清單書目收藏:0
近幾年的研究發現在真核生物中,去氧核醣核酸的甲基化跟染色質蛋白的修飾是調控基因表現的最主要兩種附基因體調控機制。在這篇論文中首先我先用bisulfite 定序跟染色質體沉澱法證實了小鼠的p53,c-myc,c-fos和r-ras這些有表現的基因在基因體結構組成上分成兩個區域:區域一是去氧核醣核酸沒有甲基化和乙醯化的染色質蛋白和附著低度的染色質蛋白H2B/2A所構成的對核酸酶敏感的區域,而區域二是甲基化去氧核醣核酸和無乙醯化的染色質蛋白和附著高度的染色質蛋白H2B/2A所構成的對核酸酶不敏感的區域。其次,我又利用染色質體沉澱法發現CTCF,PARP 1,topoisomerase,Brg 1,HDAC 1和Dnmt 1這些附基因體調控因子能夠附著在這些有表現基因的啟動子區域和在這些基因的附基因體結構上的這兩個區域之間的邊界區域中。在我的研究中利用染色質沉澱法和染色體結構補獲法也發現在有絲分裂的細胞中會因為染色質蛋白H1附著在區域二形成高等結構而導致進行的RNA 鏈鎖聚合酶在這個區域中停留,而相反地在區域一中還保留其原本結構且RNA 鏈鎖聚合酶在此區域也不會受到影響進行轉錄的進行。另外,我加入PARP 1,topoisermase和HDAC 1的抑制劑到PT 67細胞中發現到這些基因的區域二結構也能夠影響RNA 鏈鎖聚合酶的進行。總合這些實驗的結果我得到一個新的理論就是這些調控附基因體因子會附著在有表現的基因上而形成兩個附基因體結構區域,而其中區域二會調控RNA 鏈鎖聚合酶的進行,區域一它則提供一個調控基因的記億體機制系統,能夠使得調控這些基因的轉錄因子跟RNA 鏈鎖聚合酶在細胞週期中不必重新運轉跟附著。
DNA methylation and histone modifications constitute the major epigenetic control mechanism of gene expression in eukaryotic cells. In this thesis, I first analyzed the organization of epigenetic domains of mouse p53 and four active genes by bisulfite sequences and ChIP techniques and showed that these genes were organized into two major epigenetic chromatin domains with differential histone modifications, DNA methylation and nuclease sensitivity. Second, I found that CTCF, PARP 1, topoisomerases, HDAC 1 and Dnmt 1 were associated with the promoter and the intron near the boundary of epigenetic domains. In mitotic cells, RNA polymerase II is depleted in domain II of p53 gene which is folded into higher order structure and associated with H1 histone whereas domain I conformation as preserved. Similar results were obtained in other four active genes in mitotic cells. Inhibition of PARP 1, HDAC 1, Topo II and Topo I also caused the premature transcription termination. The DNA sequence of intronic region of p53 gene containing CTCF binding site was found to exhibit strong enhancer activity. These results suggest the p53 and active genes are organized into novel epigenetic domains and the regulatory factors bound at the domain boundary are involved in the regulation of transcription elongation into the methylated chromatin domain. These results also suggest that depletion of RNA polymerase II is the result of physical barrier due to folding of chromatin in domain II. The novel chromatin structure in the first domain during mitosis also
suggests a mechanism for marking active genes in successive cell cycles.
摘要-------------------------------------------------------------------------------1
Abstract--------------------------------------------------------------------------2
Introduction---------------------------------------------------------------------3
DNA methylation-------------------------------------------------------------------------------4
Histone modification---------------------------------------------------------------------------6
The interplay between DNA methylation and histone modification in gene transcriptional regulation-----------------------------------------------------------------------8
A role for Insulators in nuclear organization for gene regulation------------------------10
Aim-----------------------------------------------------------------------------------------------12
Methods and Materials-----------------------------------------------------------------13
Results-----------------------------------------------------------------------------------------23
p53 gene contains two epigenetic domains with differential DNA methylation characteristic------------------------------------------------------------------------------------23
c-myc, c-fos, r-ras and ran also contain two DNA methylation epigenetic domains whereas silenced N-myc and Lmyc1 genes are fully methylated-------------------------24
Differential histone modification patterns associated with DNA methylation domains------------------------------------------------------------------------------------------25
Unmethylated epigenetic domain I in p53 gene is hypersensitive to nuclease and deficient in H2a/H2b---------------------------------------------------------------------------27
Unmethylated epigenetic domain I in active genes is hypersensitive to nuclease digestion-----------------------------------------------------------------------------------------28
Association of CTCF with both promoter and intragenic region of p53---------------29
PARP 1 colocalized with CTCF binding region-------------------------------------------30
Brg1 localized at boundary region in p53 gene--------------------------------------------31
Dnmt1 and HDAC1 colocalization in the p53 gene---------------------------------------31
Association of topoisomerase with the boundary region of p53 gene------------------32
Association of chromatin modification factors with epigenetic domains of active genes but not with inactive genes ------------------------------------------------------------32
Depletion of RNA polymerase II in epigenetic domain II of p53 gene in mitotic arrested cells with loss of regulatory factors from the methylated epigenetic domain-------------------------------------------------------------------------------------------33
Depletion of RNA polymerase II in epigenetic domain II of c-myc gene in mitotic arrested cells with loss of regulatory factors from the methylated epigenetic domain-------------------------------------------------------------------------------------------35
Inhibition of PARP1 resulted in the depletion of RNA polymerase in the epigenetic domain II and loss of regulatory factors----------------------------------------------------36
Inhibition of topoisomerases resulted in the depletion of RNA polymerase in the epigenetic domain II and loss of regulatory factors---------------------------------------36
Opposite effect of trichostatin A on transcription of p53 and c-myc versus c-fos and r-ras----------------------------------------------------------------------------------------------37
Association of histone H1 with epigenetic domain II of p53 chromatin during blocking of transcription elongation---------------------------------------------------------38
Change of higher order chromatin structure in epigenetic domain II and preservation of extended conformation and active histone modification codes of epigenetic domain I in mitotic cells and in cells treated with inhibitors---------------------------------------39
Enhancer activity of sequence at the intronic regulatory factor binding region--------40
Discussions-----------------------------------------------------------------------------------42
Figures-----------------------------------------------------------------------------------------50
Tables-------------------------------------------------------------------------------------------93
References-----------------------------------------------------------------------------------110
1. Adelman, K., M. T. Marr, J. Werner, A. Saunders, Z. Ni, E. D. Andrulis, and J. T. Lis. 2005. Efficient release from promoter-proximal stall sites requires transcript cleavage factor TFIIS. Mol. Cell 17:103-112.
2. Akiyama, Y., C. Maesawa, S. Ogasawara, M. Terashima, and T. Masuda. 2003. Cell-type-specific repression of the maspin gene is disrupted frequently by demethylation at the promoter region in gastric intestinal metaplasia and cancer cells. Am. J. Pathol. 163:1911-1919.
3. Armstrong, J. A. 2007. Negotiating the nucleosome: factors that allow RNA polymerase II to elongate through chromatin. Biochem. Cell Biol. 85:426-434.
4. Bachman, K. E., B. H. Park, I. Rhee, H. Rajagopalan, J. G. Herman, S. B. Baylin, K. W. Kinzler, and B. Vogelstein. 2003. Histone modifications and silencing prior to DNA methylation of a tumor suppressor gene. Cancer Cell 3:89-95.
5. Bash, R., H. Wang, C. Anderson, J. Yodh, G. Hager, S. M. Lindsay, and D. Lohr. 2006. AFM imaging of protein movements: histone H2A-H2B release during nucleosome remodeling. FEBS Lett. 580:4757-4761.
6. Baylin, S. and T. H. Bestor. 2002. Altered methylation patterns in cancer cell genomes: cause or consequence? Cancer Cell 1:299-305.
7. Bird, A. 2002. DNA methylation patterns and epigenetic memory. Genes Dev. 16:6-21.
8. Bird, A. P. and A. P. Wolffe. 1999. Methylation-induced repression--belts, braces, and chromatin. Cell 99:451-454.
9. Boulikas, T., J. M. Wiseman, and W. T. Garrard. 1980. Points of contact between histone H1 and the histone octamer. Proc. Natl. Acad. Sci. U. S. A 77:127-131.
10. Brown, D. T. 2003. Histone H1 and the dynamic regulation of chromatin function. Biochem. Cell Biol. 81:221-227.
11. Burden, D. A. and N. Osheroff. 1998. Mechanism of action of eukaryotic topoisomerase II and drugs targeted to the enzyme. Biochim. Biophys. Acta 1400:139-154.
12. Cadieux, B., T. T. Ching, S. R. VandenBerg, and J. F. Costello. 2006. Genome-wide hypomethylation in human glioblastomas associated with specific copy number alteration, methylenetetrahydrofolate reductase allele status, and increased proliferation. Cancer Res. 66:8469-8476.
13. Cameron, E. E., K. E. Bachman, S. Myohanen, J. G. Herman, and S. B. Baylin. 1999. Synergy of demethylation and histone deacetylase inhibition in the re-expression of genes silenced in cancer. Nat. Genet. 21:103-107.
14. Chan, H. W., J. S. Miller, M. B. Moore, and C. T. Lutz. 2005. Epigenetic control of highly homologous killer Ig-like receptor gene alleles. J. Immunol. 175:5966-5974.
15. Chen, L., L. Smith, M. R. Johnson, K. Wang, R. B. Diasio, and J. B. Smith. 2000. Activation of protein kinase C induces nuclear translocation of RFX1 and down-regulates c-myc via an intron 1 X box in undifferentiated leukemia HL-60 cells. J. Biol. Chem. 275:32227-32233.
16. Cheung, P., C. D. Allis, and P. Sassone-Corsi. 2000. Signaling to chromatin through histone modifications. Cell 103:263-271.
17. Chirinos, M., F. Hernandez, and E. Palacian. 1999. Transcription of DNA templates associated with histone (H3 x H4)(2) tetramers. Arch. Biochem. Biophys. 370:222-230.
18. Cui, R., H. R. Widlund, E. Feige, J. Y. Lin, D. L. Wilensky, V. E. Igras, J. D'Orazio, C. Y. Fung, C. F. Schanbacher, S. R. Granter, and D. E. Fisher. 2007. Central role of p53 in the suntan response and pathologic hyperpigmentation. Cell 128:853-864.
19. De, S. C., B. O. De, I. Faraoni, C. Lurquin, F. Brasseur, and T. Boon. 1996. The activation of human gene MAGE-1 in tumor cells is correlated with genome-wide demethylation. Proc. Natl. Acad. Sci. U. S. A 93:7149-7153.
20. Dekker, J., K. Rippe, M. Dekker, and N. Kleckner. 2002. Capturing chromosome conformation. Science 295:1306-1311.
21. Dillon, N. and F. Grosveld. 1994. Chromatin domains as potential units of eukaryotic gene function. Curr. Opin. Genet. Dev. 4:260-264.
22. Drolet, M. 2006. Growth inhibition mediated by excess negative supercoiling: the interplay between transcription elongation, R-loop formation and DNA topology. Mol. Microbiol. 59:723-730.
23. Ehrlich, M., M. A. Gama-Sosa, L. H. Huang, R. M. Midgett, K. C. Kuo, R. A. McCune, and C. Gehrke. 1982. Amount and distribution of 5-methylcytosine in human DNA from different types of tissues of cells. Nucleic Acids Res. 10:2709-2721.
24. El-Kady, A. and E. Klenova. 2005. Regulation of the transcription factor, CTCF, by phosphorylation with protein kinase CK2. FEBS Lett. 579:1424-1434.
25. Enver, T., A. C. Brewer, and R. K. Patient. 1985. Simian virus 40-mediated cis induction of the Xenopus beta-globin DNase I hypersensitive site. Nature 318:680-683.
26. Espada, J. and M. Esteller. 2007. Epigenetic control of nuclear architecture. Cell Mol. Life Sci. 64:449-457.
27. Esteller, M. 2008. Epigenetics in cancer. N. Engl. J. Med. 358:1148-1159.
28. Feinberg, A. P., R. Ohlsson, and S. Henikoff. 2006. The epigenetic progenitor origin of human cancer. Nat. Rev. Genet. 7:21-33.
29. Filippova, G. N., C. F. Qi, J. E. Ulmer, J. M. Moore, M. D. Ward, Y. J. Hu, D. I. Loukinov, E. M. Pugacheva, E. M. Klenova, P. E. Grundy, A. P. Feinberg, A. M. Cleton-Jansen, E. W. Moerland, C. J. Cornelisse, H. Suzuki, A. Komiya, A. Lindblom, F. Dorion-Bonnet, P. E. Neiman, H. C. Morse, III, S. J. Collins, and V. V. Lobanenkov. 2002. Tumor-associated zinc finger mutations in the CTCF transcription factor selectively alter tts DNA-binding specificity. Cancer Res. 62:48-52.
30. Flaxenburg, J. A., M. Melter, P. H. Lapchak, D. M. Briscoe, and S. Pal. 2004. The CD40-induced signaling pathway in endothelial cells resulting in the overexpression of vascular endothelial growth factor involves Ras and phosphatidylinositol 3-kinase. J. Immunol. 172:7503-7509.
31. Fuks, F., P. J. Hurd, R. Deplus, and T. Kouzarides. 2003. The DNA methyltransferases associate with HP1 and the SUV39H1 histone methyltransferase. Nucleic Acids Res. 31:2305-2312.
32. Fuks, F., P. J. Hurd, R. Deplus, and T. Kouzarides. 2003. The DNA methyltransferases associate with HP1 and the SUV39H1 histone methyltransferase. Nucleic Acids Res. 31:2305-2312.
33. Gaszner, M. and G. Felsenfeld. 2006. Insulators: exploiting transcriptional and epigenetic mechanisms. Nat. Rev. Genet. 7:703-713.
34. Gaudet, F., J. G. Hodgson, A. Eden, L. Jackson-Grusby, J. Dausman, J. W. Gray, H. Leonhardt, and R. Jaenisch. 2003. Induction of tumors in mice by genomic hypomethylation. Science 300:489-492.
35. Gombert, W. M., S. D. Farris, E. D. Rubio, K. M. Morey-Rosler, W. H. Schubach, and A. Krumm. 2003. The c-myc insulator element and matrix attachment regions define the c-myc chromosomal domain. Mol. Cell Biol. 23:9338-9348.
36. Gonzalez-Zulueta, M., C. M. Bender, A. S. Yang, T. Nguyen, R. W. Beart, J. M. Van Tornout, and P. A. Jones. 1995. Methylation of the 5' CpG island of the p16/CDKN2 tumor suppressor gene in normal and transformed human tissues correlates with gene silencing. Cancer Res. 55:4531-4535.
37. Greger, V., N. Debus, D. Lohmann, W. Hopping, E. Passarge, and B. Horsthemke. 1994. Frequency and parental origin of hypermethylated RB1 alleles in retinoblastoma. Hum. Genet. 94:491-496.
38. Guil, S. and M. Esteller. 2009. DNA methylomes, histone codes and miRNAs: Tying it all together. Int. J. Biochem. Cell Biol. 41:87-95.
39. Haince, J. F., M. Rouleau, and G. G. Poirier. 2006. Transcription. Gene expression needs a break to unwind before carrying on. Science 312:1752-1753.
40. Hannan, R. D., A. Cavanaugh, W. M. Hempel, T. Moss, and L. Rothblum. 1999. Identification of a mammalian RNA polymerase I holoenzyme containing components of the DNA repair/replication system. Nucleic Acids Res. 27:3720-3727.
41. Hansen, J. C. and A. P. Wolffe. 1994. A role for histones H2A/H2B in chromatin folding and transcriptional repression. Proc. Natl. Acad. Sci. U. S. A 91:2339-2343.
42. Hatton, K. S., K. Mahon, L. Chin, F. C. Chiu, H. W. Lee, D. Peng, S. D. Morgenbesser, J. Horner, and R. A. DePinho. 1996. Expression and activity of L-Myc in normal mouse development. Mol. Cell Biol. 16:1794-1804.
43. Hegi, M. E., A. C. Diserens, T. Gorlia, M. F. Hamou, T. N. de, M. Weller, J. M. Kros, J. A. Hainfellner, W. Mason, L. Mariani, J. E. Bromberg, P. Hau, R. O. Mirimanoff, J. G. Cairncross, R. C. Janzer, and R. Stupp. 2005. MGMT gene silencing and benefit from temozolomide in glioblastoma. N. Engl. J. Med. 352:997-1003.
44. Hiltunen, M. O., L. Alhonen, J. Koistinaho, S. Myohanen, M. Paakkonen, S. Marin, V. M. Kosma, and J. Janne. 1997. Hypermethylation of the APC (adenomatous polyposis coli) gene promoter region in human colorectal carcinoma. Int. J. Cancer 70:644-648.
45. Himes, S. R., H. Tagoh, N. Goonetilleke, T. Sasmono, D. Oceandy, R. Clark, C. Bonifer, and D. A. Hume. 2001. A highly conserved c-fms gene intronic element controls macrophage-specific and regulated expression. J. Leukoc. Biol. 70:812-820.
46. Hoffmann, M. J. and W. A. Schulz. 2005. Causes and consequences of DNA hypomethylation in human cancer. Biochem. Cell Biol. 83:296-321.
47. Horn, P. J., K. A. Crowley, L. M. Carruthers, J. C. Hansen, and C. L. Peterson. 2002. The SIN domain of the histone octamer is essential for intramolecular folding of nucleosomal arrays. Nat. Struct. Biol. 9:167-171.
48. Horn, P. J. and C. L. Peterson. 2002. Molecular biology. Chromatin higher order folding--wrapping up transcription. Science 297:1824-1827.
49. Jenuwein, T. 2006. The epigenetic magic of histone lysine methylation. FEBS J. 273:3121-3135.
50. Jones, P. A. and S. B. Baylin. 2007. The epigenomics of cancer. Cell 128:683-692.
51. Khobta, A., F. Ferri, L. Lotito, A. Montecucco, R. Rossi, and G. Capranico. 2006. Early effects of topoisomerase I inhibition on RNA polymerase II along transcribed genes in human cells. J. Mol. Biol. 357:127-138.
52. Kidder, B. L., S. Palmer, and J. G. Knott. 2008. SWI/SNF-Brg1 Regulates Self-Renewal and Occupies Core Pluripotency-Related Genes in Embryonic Stem Cells. Stem Cells.
53. Kireeva, M. L., W. Walter, V. Tchernajenko, V. Bondarenko, M. Kashlev, and V. M. Studitsky. 2002. Nucleosome remodeling induced by RNA polymerase II: loss of the H2A/H2B dimer during transcription. Mol. Cell 9:541-552.
54. Kizer, K. O., H. P. Phatnani, Y. Shibata, H. Hall, A. L. Greenleaf, and B. D. Strahl. 2005. A novel domain in Set2 mediates RNA polymerase II interaction and couples histone H3 K36 methylation with transcript elongation. Mol. Cell Biol. 25:3305-3316.
55. Klenova, E. and R. Ohlsson. 2005. Poly(ADP-ribosyl)ation and epigenetics. Is CTCF PARt of the plot? Cell Cycle 4:96-101.
56. Klose, R. J., K. Yamane, Y. Bae, D. Zhang, H. Erdjument-Bromage, P. Tempst, J. Wong, and Y. Zhang. 2006. The transcriptional repressor JHDM3A demethylates trimethyl histone H3 lysine 9 and lysine 36. Nature 442:312-316.
57. Kondo, E., Z. Gu, A. Horii, and S. Fukushige. 2005. The thymine DNA glycosylase MBD4 represses transcription and is associated with methylated p16(INK4a) and hMLH1 genes. Mol. Cell Biol. 25:4388-4396.
58. Kosak, S. T. and M. Groudine. 2004. Form follows function: The genomic organization of cellular differentiation. Genes Dev. 18:1371-1384.
59. Kouzarides, T. 2007. Chromatin modifications and their function. Cell 128:693-705.
60. Kraus, W. L. and J. T. Lis. 2003. PARP goes transcription. Cell 113:677-683.
61. Kretzschmar, M., M. Meisterernst, and R. G. Roeder. 1993. Identification of human DNA topoisomerase I as a cofactor for activator-dependent transcription by RNA polymerase II. Proc. Natl. Acad. Sci. U. S. A 90:11508-11512.
62. Kulaeva, O. I., D. A. Gaykalova, and V. M. Studitsky. 2007. Transcription through chromatin by RNA polymerase II: histone displacement and exchange. Mutat. Res. 618:116-129.
63. Kurukuti, S., V. K. Tiwari, G. Tavoosidana, E. Pugacheva, A. Murrell, Z. Zhao, V. Lobanenkov, W. Reik, and R. Ohlsson. 2006. CTCF binding at the H19 imprinting control region mediates maternally inherited higher-order chromatin conformation to restrict enhancer access to Igf2. Proc. Natl. Acad. Sci. U. S. A 103:10684-10689.
64. Laemmli, U. K., E. Kas, L. Poljak, and Y. Adachi. 1992. Scaffold-associated regions: cis-acting determinants of chromatin structural loops and functional domains. Curr. Opin. Genet. Dev. 2:275-285.
65. Lehnertz, B., Y. Ueda, A. A. Derijck, U. Braunschweig, L. Perez-Burgos, S. Kubicek, T. Chen, E. Li, T. Jenuwein, and A. H. Peters. 2003. Suv39h-mediated histone H3 lysine 9 methylation directs DNA methylation to major satellite repeats at pericentric heterochromatin. Curr. Biol. 13:1192-1200.
66. Lehnertz, B., Y. Ueda, A. A. Derijck, U. Braunschweig, L. Perez-Burgos, S. Kubicek, T. Chen, E. Li, T. Jenuwein, and A. H. Peters. 2003. Suv39h-mediated histone H3 lysine 9 methylation directs DNA methylation to major satellite repeats at pericentric heterochromatin. Curr. Biol. 13:1192-1200.
67. Lehnertz, B., Y. Ueda, A. A. Derijck, U. Braunschweig, L. Perez-Burgos, S. Kubicek, T. Chen, E. Li, T. Jenuwein, and A. H. Peters. 2003. Suv39h-mediated histone H3 lysine 9 methylation directs DNA methylation to major satellite repeats at pericentric heterochromatin. Curr. Biol. 13:1192-1200.
68. Levchenko, V., B. Jackson, and V. Jackson. 2005. Histone release during transcription: displacement of the two H2A-H2B dimers in the nucleosome is dependent on different levels of transcription-induced positive stress. Biochemistry 44:5357-5372.
69. Li, E. 2002. Chromatin modification and epigenetic reprogramming in mammalian development. Nat. Rev. Genet. 3:662-673.
70. Liebich, I., J. Bode, I. Reuter, and E. Wingender. 2002. Evaluation of sequence motifs found in scaffold/matrix-attached regions (S/MARs). Nucleic Acids Res. 30:3433-3442.
71. Liu, H., J. Wang, and E. M. Epner. 2004. Cyclin D1 activation in B-cell malignancy: association with changes in histone acetylation, DNA methylation, and RNA polymerase II binding to both promoter and distal sequences. Blood 104:2505-2513.
72. Lovett, B. D., N. L. Lo, E. F. Rappaport, I. A. Blair, N. Osheroff, N. Zheng, M. D. Megonigal, W. R. Williams, P. C. Nowell, and C. A. Felix. 2001. Near-precise interchromosomal recombination and functional DNA topoisomerase II cleavage sites at MLL and AF-4 genomic breakpoints in treatment-related acute lymphoblastic leukemia with t(4;11) translocation. Proc. Natl. Acad. Sci. U. S. A 98:9802-9807.
73. Martin, C. and Y. Zhang. 2005. The diverse functions of histone lysine methylation. Nat. Rev. Mol. Cell Biol. 6:838-849.
74. Matlashewski, G., P. Lamb, D. Pim, J. Peacock, L. Crawford, and S. Benchimol. 1984. Isolation and characterization of a human p53 cDNA clone: expression of the human p53 gene. EMBO J. 3:3257-3262.
75. Metzger, E., M. Wissmann, N. Yin, J. M. Muller, R. Schneider, A. H. Peters, T. Gunther, R. Buettner, and R. Schule. 2005. LSD1 demethylates repressive histone marks to promote androgen-receptor-dependent transcription. Nature 437:436-439.
76. Millar, D. S., C. L. Paul, P. L. Molloy, and S. J. Clark. 2000. A distinct sequence (ATAAA)n separates methylated and unmethylated domains at the 5'-end of the GSTP1 CpG island. J. Biol. Chem. 275:24893-24899.
77. Mondal, N., Y. Zhang, Z. Jonsson, S. K. Dhar, M. Kannapiran, and J. D. Parvin. 2003. Elongation by RNA polymerase II on chromatin templates requires topoisomerase activity. Nucleic Acids Res. 31:5016-5024.
78. Moon, H., G. Filippova, D. Loukinov, E. Pugacheva, Q. Chen, S. T. Smith, A. Munhall, B. Grewe, M. Bartkuhn, R. Arnold, L. J. Burke, R. Renkawitz-Pohl, R. Ohlsson, J. Zhou, R. Renkawitz, and V. Lobanenkov. 2005. CTCF is conserved from Drosophila to humans and confers enhancer blocking of the Fab-8 insulator. EMBO Rep. 6:165-170.
79. Morris, S. A., Y. Shibata, K. Noma, Y. Tsukamoto, E. Warren, B. Temple, S. I. Grewal, and B. D. Strahl. 2005. Histone H3 K36 methylation is associated with transcription elongation in Schizosaccharomyces pombe. Eukaryot. Cell 4:1446-1454.
80. Nakamura, N. and K. Takenaga. 1998. Hypomethylation of the metastasis-associated S100A4 gene correlates with gene activation in human colon adenocarcinoma cell lines. Clin. Exp. Metastasis 16:471-479.
81. Nakayama, J., J. C. Rice, B. D. Strahl, C. D. Allis, and S. I. Grewal. 2001. Role of histone H3 lysine 9 methylation in epigenetic control of heterochromatin assembly. Science 292:110-113.
82. Nemeth, A. and G. Langst. 2004. Chromatin higher order structure: opening up chromatin for transcription. Brief. Funct. Genomic. Proteomic. 2:334-343.
83. Ng, R. K. and J. B. Gurdon. 2008. Epigenetic memory of an active gene state depends on histone H3.3 incorporation into chromatin in the absence of transcription. Nat. Cell Biol. 10:102-109.
84. Nishigaki, M., K. Aoyagi, I. Danjoh, M. Fukaya, K. Yanagihara, H. Sakamoto, T. Yoshida, and H. Sasaki. 2005. Discovery of aberrant expression of R-RAS by cancer-linked DNA hypomethylation in gastric cancer using microarrays. Cancer Res. 65:2115-2124.
85. Ohlsson, R., R. Renkawitz, and V. Lobanenkov. 2001. CTCF is a uniquely versatile transcription regulator linked to epigenetics and disease. Trends Genet. 17:520-527.
86. Okano, M., D. W. Bell, D. A. Haber, and E. Li. 1999. DNA methyltransferases Dnmt3a and Dnmt3b are essential for de novo methylation and mammalian development. Cell 99:247-257.
87. Ozsolak, F., J. S. Song, X. S. Liu, and D. E. Fisher. 2007. High-throughput mapping of the chromatin structure of human promoters. Nat. Biotechnol. 25:244-248.
88. Pal, S., K. Datta, and D. Mukhopadhyay. 2001. Central role of p53 on regulation of vascular permeability factor/vascular endothelial growth factor (VPF/VEGF) expression in mammary carcinoma. Cancer Res. 61:6952-6957.
89. Parsons, G. G. and C. A. Spencer. 1997. Mitotic repression of RNA polymerase II transcription is accompanied by release of transcription elongation complexes. Mol. Cell Biol. 17:5791-5802.
90. Patrone, G., F. Puppo, R. Cusano, M. Scaranari, I. Ceccherini, A. Puliti, and R. Ravazzolo. 2000. Nuclear run-on assay using biotin labeling, magnetic bead capture and analysis by fluorescence-based RT-PCR. Biotechniques 29:1012-1017.
91. Paulin, R., G. W. Grigg, M. W. Davey, and A. A. Piper. 1998. Urea improves efficiency of bisulphite-mediated sequencing of 5'-methylcytosine in genomic DNA. Nucleic Acids Res. 26:5009-5010.
92. Pinaud, S. and J. Mirkovitch. 1998. Regulation of c-fos expression by RNA polymerase elongation competence. J. Mol. Biol. 280:785-798.
93. Plet, A., D. Eick, and J. M. Blanchard. 1995. Elongation and premature termination of transcripts initiated from c-fos and c-myc promoters show dissimilar patterns. Oncogene 10:319-328.
94. Plou, F. J., M. A. Cruces, M. Ferrer, G. Fuentes, E. Pastor, M. Bernabe, M. Christensen, F. Comelles, J. L. Parra, and A. Ballesteros. 2002. Enzymatic acylation of di- and trisaccharides with fatty acids: choosing the appropriate enzyme, support and solvent. J. Biotechnol. 96:55-66.
95. Pradhan, S., D. Talbot, M. Sha, J. Benner, L. Hornstra, E. Li, R. Jaenisch, and R. J. Roberts. 1997. Baculovirus-mediated expression and characterization of the full-length murine DNA methyltransferase. Nucleic Acids Res. 25:4666-4673.
96. Radonjic, M., J. C. Andrau, P. Lijnzaad, P. Kemmeren, T. T. Kockelkorn, L. D. van, N. L. van Berkum, and F. C. Holstege. 2005. Genome-wide analyses reveal RNA polymerase II located upstream of genes poised for rapid response upon S. cerevisiae stationary phase exit. Mol. Cell 18:171-183.
97. Ramachandran, A., M. Omar, P. Cheslock, and G. R. Schnitzler. 2003. Linker histone H1 modulates nucleosome remodeling by human SWI/SNF. J. Biol. Chem. 278:48590-48601.
98. Razin, S. V., C. M. Farrell, and F. Recillas-Targa. 2003. Genomic domains and regulatory elements operating at the domain level. Int. Rev. Cytol. 226:63-125.
99. Razin, S. V., O. V. Iarovaia, N. Sjakste, T. Sjakste, L. Bagdoniene, A. V. Rynditch, E. R. Eivazova, M. Lipinski, and Y. S. Vassetzky. 2007. Chromatin domains and regulation of transcription. J. Mol. Biol. 369:597-607.
100. Rea, S., F. Eisenhaber, D. O'Carroll, B. D. Strahl, Z. W. Sun, M. Schmid, S. Opravil, K. Mechtler, C. P. Ponting, C. D. Allis, and T. Jenuwein. 2000. Regulation of chromatin structure by site-specific histone H3 methyltransferases. Nature 406:593-599.
101. Richard-Foy, H. and G. L. Hager. 1987. Sequence-specific positioning of nucleosomes over the steroid-inducible MMTV promoter. EMBO J. 6:2321-2328.
102. Robertson, K. D., S. it-Si-Ali, T. Yokochi, P. A. Wade, P. L. Jones, and A. P. Wolffe. 2000. DNMT1 forms a complex with Rb, E2F1 and HDAC1 and represses transcription from E2F-responsive promoters. Nat. Genet. 25:338-342.
103. Rollins, R. A., F. Haghighi, J. R. Edwards, R. Das, M. Q. Zhang, J. Ju, and T. H. Bestor. 2006. Large-scale structure of genomic methylation patterns. Genome Res. 16:157-163.
104. Ryser, S., T. Fujita, S. Tortola, I. Piuz, and W. Schlegel. 2007. The rate of c-fos transcription in vivo is continuously regulated at the level of elongation by dynamic stimulus-coupled recruitment of positive transcription elongation factor b. J. Biol. Chem. 282:5075-5084.
105. Sakai, T., J. Toguchida, N. Ohtani, D. W. Yandell, J. M. Rapaport, and T. P. Dryja. 1991. Allele-specific hypermethylation of the retinoblastoma tumor-suppressor gene. Am. J. Hum. Genet. 48:880-888.
106. Shann, Y. J., C. Cheng, C. H. Chiao, D. T. Chen, P. H. Li, and M. T. Hsu. 2008. Genome-wide mapping and characterization of hypomethylated sites in human tissues and breast cancer cell lines. Genome Res. 18:791-801.
107. Shi, Y., F. Lan, C. Matson, P. Mulligan, J. R. Whetstine, P. A. Cole, R. A. Casero, and Y. Shi. 2004. Histone demethylation mediated by the nuclear amine oxidase homolog LSD1. Cell 119:941-953.
108. Simonis, M., J. Kooren, and L. W. de. 2007. An evaluation of 3C-based methods to capture DNA interactions. Nat. Methods 4:895-901.
109. Singh, M., G. M. Popowicz, M. Krajewski, and T. A. Holak. 2007. Structural ramification for acetyl-lysine recognition by the bromodomain of human BRG1 protein, a central ATPase of the SWI/SNF remodeling complex. Chembiochem. 8:1308-1316.
110. Soares, J., A. E. Pinto, C. V. Cunha, S. Andre, I. Barao, J. M. Sousa, and M. Cravo. 1999. Global DNA hypomethylation in breast carcinoma: correlation with prognostic factors and tumor progression. Cancer 85:112-118.
111. Spencer, C. A., M. J. Kruhlak, H. L. Jenkins, X. Sun, and D. P. Bazett-Jones. 2000. Mitotic transcription repression in vivo in the absence of nucleosomal chromatin condensation. J. Cell Biol. 150:13-26.
112. Sproul, D., N. Gilbert, and W. A. Bickmore. 2005. The role of chromatin structure in regulating the expression of clustered genes. Nat. Rev. Genet. 6:775-781.
113. Stanton, B. R., A. S. Perkins, L. Tessarollo, D. A. Sassoon, and L. F. Parada. 1992. Loss of N-myc function results in embryonic lethality and failure of the epithelial component of the embryo to develop. Genes Dev. 6:2235-2247.
114. Suzuki, H., D. N. Watkins, K. W. Jair, K. E. Schuebel, S. D. Markowitz, W. D. Chen, T. P. Pretlow, B. Yang, Y. Akiyama, E. M. Van, M. Toyota, T. Tokino, Y. Hinoda, K. Imai, J. G. Herman, and S. B. Baylin. 2004. Epigenetic inactivation of SFRP genes allows constitutive WNT signaling in colorectal cancer. Nat. Genet. 36:417-422.
115. Tan-Wong, S. M., J. D. French, N. J. Proudfoot, and M. A. Brown. 2008. Dynamic interactions between the promoter and terminator regions of the mammalian BRCA1 gene. Proc. Natl. Acad. Sci. U. S. A 105:5160-5165.
116. Teitz, T., T. Wei, M. B. Valentine, E. F. Vanin, J. Grenet, V. A. Valentine, F. G. Behm, A. T. Look, J. M. Lahti, and V. J. Kidd. 2000. Caspase 8 is deleted or silenced preferentially in childhood neuroblastomas with amplification of MYCN. Nat. Med. 6:529-535.
117. Tomatsu, S., K. O. Orii, M. R. Islam, G. N. Shah, J. H. Grubb, K. Sukegawa, Y. Suzuki, T. Orii, N. Kondo, and W. S. Sly. 2002. Methylation patterns of the human beta-glucuronidase gene locus: boundaries of methylation and general implications for frequent point mutations at CpG dinucleotides. Genomics 79:363-375.
118. Valadez-Graham, V., S. V. Razin, and F. Recillas-Targa. 2004. CTCF-dependent enhancer blockers at the upstream region of the chicken alpha-globin gene domain. Nucleic Acids Res. 32:1354-1362.
119. Valenzuela, L. and R. T. Kamakaka. 2006. Chromatin insulators. Annu. Rev. Genet. 40:107-138.
120. Ventura, A., D. G. Kirsch, M. E. McLaughlin, D. A. Tuveson, J. Grimm, L. Lintault, J. Newman, E. E. Reczek, R. Weissleder, and T. Jacks. 2007. Restoration of p53 function leads to tumour regression in vivo. Nature 445:661-665.
121. Vicent, G. P., A. S. Nacht, C. L. Smith, C. L. Peterson, S. Dimitrov, and M. Beato. 2004. DNA instructed displacement of histones H2A and H2B at an inducible promoter. Mol. Cell 16:439-452.
122. Wei, Y., L. Yu, J. Bowen, M. A. Gorovsky, and C. D. Allis. 1999. Phosphorylation of histone H3 is required for proper chromosome condensation and segregation. Cell 97:99-109.
123. West, A. G., M. Gaszner, and G. Felsenfeld. 2002. Insulators: many functions, many mechanisms. Genes Dev. 16:271-288.
124. Worcel, A., S. Han, and M. L. Wong. 1978. Assembly of newly replicated chromatin. Cell 15:969-977.
125. Wright, S., L. F. Mirels, M. C. Calayag, and J. M. Bishop. 1991. Premature termination of transcription from the P1 promoter of the mouse c-myc gene. Proc. Natl. Acad. Sci. U. S. A 88:11383-11387.
126. Wu, H. Y., S. H. Shyy, J. C. Wang, and L. F. Liu. 1988. Transcription generates positively and negatively supercoiled domains in the template. Cell 53:433-440.
127. Xin, L., G. L. Zhou, W. Song, X. S. Wu, G. H. Wei, D. L. Hao, X. Lv, D. P. Liu, and C. C. Liang. 2007. Exploring cellular memory molecules marking competent and active transcriptions. BMC. Mol. Biol. 8:31.
128. Yoon, Y. S., S. Jeong, Q. Rong, K. Y. Park, J. H. Chung, and K. Pfeifer. 2007. Analysis of the H19ICR insulator. Mol. Cell Biol. 27:3499-3510.
129. Yuan, W. 2000. Intron 1 rather than 5' flanking sequence mediates cell type-specific expression of c-myb at level of transcription elongation. Biochim. Biophys. Acta 1490:74-86.
130. Yusufzai, T. M., H. Tagami, Y. Nakatani, and G. Felsenfeld. 2004. CTCF tethers an insulator to subnuclear sites, suggesting shared insulator mechanisms across species. Mol. Cell 13:291-298.
131. Zilberman, D. and S. Henikoff. 2007. Genome-wide analysis of DNA methylation patterns. Development 134:3959-3965.
QRCODE
 
 
 
 
 
                                                                                                                                                                                                                                                                                                                                                                                                               
第一頁 上一頁 下一頁 最後一頁 top
無相關期刊