생명과학회지 (Journal of Life Science)

  • 제21권4호
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  • Pages.616-620
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  • 2011
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  • 1225-9918(pISSN)
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  • 2287-3406(eISSN)
한국생명과학회 (Korean Society of Life Science)
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히스톤 H3K27 변형과 유전자 전사

Histone H3K27 Modifications and Gene Transcription

  • 김애리 (부산대학교 자연과학대학 분자생물학과)
  • Kim, Ae-Ri (Department of Molecular Biology, College of Natural Sciences, Pusan National University)
  • 투고 : 2011.01.26
  • 심사 : 2011.02.23
  • 발행 : 2011.04.30
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초록

진핵세포의 크로마틴에서 히스톤 단백질 H3와 H4의 라이신 잔기는 공유결합에 의해 변형된다. 히스톤 H3에서 27번 라이신은 아세틸화되거나(H3K27ac) 세 가지 단계로 메틸화가 될 수 있으며(H3K27me1, H3K27me2, H3K27me3), 이러한 H3K27의 변형들은 각각 독특한 형태로 유전자 전사 및 크로마틴 구조와 관련된다. 일반적으로 H3K27ac과 H3K27me1은 좌위조절부위나 활발히 전사되는 유전자처럼 활성 크로마틴에서 나타나고, 이에 반해 전사가 일어나지 않은 유전자는 높은 수준의 H3K27me2과 H3K27me3이 관찰된다. 이러한 변형들은 각각 다른 종류의 변형효소에 의해 촉매된다. 최근 연구들은 유전자 전사 및 크로마틴 구조 형성에서 H3K27의 네 가지 변형들 사이에 상관 관계가 있음을 제시하고 있다.

Lysine residues of histone H3 and H4 are covalently modified in the chromatin of eukaryotic cells. Lysine 27 in histone H3 was acetylated (H3K27ac) or methylated at three levels; mono-, di-, and trimethylation (H3K27me1, H3K27me2, and H3K27me3). These modifications at H3K27 were related with gene transcription and/or chromatin structure in distinct patterns. Generally, H3K27ac and H3K27me1 were enriched in active chromatin, such as the locus control region or transcriptionally active genes, while transcriptionally inactive genes were highly marked by H3K27me2 and H3K27me3. These modifications appear to have been catalyzed by distinct histone-modifying enzymes. Recent studies suggest that the four kinds of modifications at H3K27 have inter-correlation in gene transcription or chromatin structure formation.

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참고문헌

  1. Barski, A., S. Cuddapah, K. Cui, T. Y. Roh, D. E. Schones, Z. Wang, G. Wei, I. Chepelev, and K. Zhao. 2007. High-resolution profiling of histone methylations in the human genome. Cell 129, 823-837. https://doi.org/10.1016/j.cell.2007.05.009
  2. Cao, R., L. Wang, H. Wang, L. Xia, H. Erdjument-Bromage, P. Tempst, R. S. Jones, and Y. Zhang. 2002. Role of histone H3 lysine 27 methylation in Polycomb-group silencing. Science 298, 1039-1043. https://doi.org/10.1126/science.1076997
  3. Cao, R. and Y. Zhang. 2004. The functions of E(Z)/EZH2-mediated methylation of lysine 27 in histone H3. Curr. Opin. Genet. Dev. 14, 155-164. https://doi.org/10.1016/j.gde.2004.02.001
  4. Chaturvedi, C., A. M. Hosey, C. Palii, C. Perez-Iratxeta, Y. Nakatani, J. A. Ranish, F. J. Dilworth, and M. Brand. 2009. Dual role for the methyltransferase G9a in the maintenance of beta-globin gene transcription in adult erythroid cells. Proc. Natl. Acad. Sci. USA. 106, 18303-18308. https://doi.org/10.1073/pnas.0906769106
  5. Chen, H., S. W. Tu, and J. T. Hsieh. 2005. Down-regulation of human DAB2IP gene expression mediated by polycomb Ezh2 complex and histone deacetylase in prostate cancer. J. Biol. Chem. 280, 22437-22444. https://doi.org/10.1074/jbc.M501379200
  6. Fujii, S., K. Ito, Y. Ito, and A. Ochiai. 2008. Enhancer of zeste homologue 2 (EZH2) down-regulates RUNX3 by increasing histone H3 methylation. J. Biol. Chem. 283, 17324-17332. https://doi.org/10.1074/jbc.M800224200
  7. Ikegami, K., M. Iwatani, M. Suzuki, M. Tachibana, Y. Shinkai, S. Tanaka, J. M. Greally, S. Yagi, N. Hattori, and K. Shiota. 2007. Genome-wide and locus-specific DNA hypomethylation in G9a deficient mouse embryonic stem cells. Genes Cells 12, 1-11. https://doi.org/10.1111/j.1365-2443.2006.01029.x
  8. Kim, A., C. M. Kiefer, and A. Dean. 2007. Distinctive signatures of histone methylation in transcribed coding and noncoding human beta-globin sequences. Mol. Cell Biol. 27, 1271-1279. https://doi.org/10.1128/MCB.01684-06
  9. Kim, A., H. Zhao, I. Ifrim, and A. Dean. 2007. Beta-globin intergenic transcription and histone acetylation dependent on an enhancer. Mol. Cell Biol. 27, 2980-2986. https://doi.org/10.1128/MCB.02337-06
  10. Kim, K. and A. Kim. 2010. Sequential changes in chromatin structure during transcriptional activation in the beta globin LCR and its target gene. Int. J. Biochem. Cell Biol. 42, 1517-1524. https://doi.org/10.1016/j.biocel.2010.05.009
  11. Kim, Y. W. and A. Kim. 2011. Characterization of histone H3K27 modifications in the ${\beta}$-globin locus. Biochem. Biophys. Res. Commun. 405, 210-215. https://doi.org/10.1016/j.bbrc.2011.01.010
  12. Kouzarides, T. 2007. Chromatin modifications and their function. Cell 128, 693-705. https://doi.org/10.1016/j.cell.2007.02.005
  13. Koyanagi, M., A. Baguet, J. Martens, R. Margueron, T. Jenuwein, and M. Bix. 2005. EZH2 and histone 3 trimethyl lysine 27 associated with Il4 and Il13 gene silencing in Th1 cells. J. Biol. Chem. 280, 31470-31477. https://doi.org/10.1074/jbc.M504766200
  14. Kuzmichev, A., K. Nishioka, H. Erdjument-Bromage, P. Tempst, and D. Reinberg. 2002. Histone methyltransferase activity associated with a human multiprotein complex containing the Enhancer of Zeste protein. Genes Dev. 16, 2893-2905. https://doi.org/10.1101/gad.1035902
  15. Montgomery, N. D., D. Yee, A. Chen, S. Kalantry, S. J. Chamberlain, A. P. Otte, and T. Magnuson. 2005. The murine polycomb group protein Eed is required for global histone H3 lysine-27 methylation. Curr. Biol. 15, 942-947. https://doi.org/10.1016/j.cub.2005.04.051
  16. Pasini, D., A. P. Bracken, M. R. Jensen, D. E. Lazzerini, and K. Helin. 2004. Suz12 is essential for mouse development and for EZH2 histone methyltransferase activity. EMBO J. 23, 4061-4071. https://doi.org/10.1038/sj.emboj.7600402
  17. Pasini, D., M. Malatesta, H. R. Jung, J. Walfridsson, A. Willer, L. Olsson, J. Skotte, A. Wutz, B. Porse, O. N. Jensen, and K. Helin. 2010. Characterization of an antagonistic switch between histone H3 lysine 27 methylation and acetylation in the transcriptional regulation of Polycomb group target genes. Nucleic Acids Res. 38, 4958-4969. https://doi.org/10.1093/nar/gkq244
  18. Peters, A. H., S. Kubicek, K. Mechtler, R. J. O'Sullivan, A. A. Derijck, L. Perez-Burgos, A. Kohlmaier, S. Opravil, M. Tachibana, Y. Shinkai, J. H. Martens, and T. Jenuwein. 2003. Partitioning and plasticity of repressive histone methylation states in mammalian chromatin. Mol. Cell 12, 1577-1589. https://doi.org/10.1016/S1097-2765(03)00477-5
  19. Schuettengruber, B., D. Chourrout, M. Vervoort, B. Leblanc, and G. Cavalli. 2007. Genome regulation by polycomb and trithorax proteins. Cell 128, 735-745 https://doi.org/10.1016/j.cell.2007.02.009
  20. Shen, X., Y. Liu, Y. J. Hsu, Y. Fujiwara, J. Kim, X. Mao, G. C. Yuan, and S. H. Orkin. 2008. EZH1 mediates methylation on histone H3 lysine 27 and complements EZH2 in maintaining stem cell identity and executing pluripotency. Mol. Cell 32, 491-502. https://doi.org/10.1016/j.molcel.2008.10.016
  21. Simon, J. A. and R. E. Kingston. 2009. Mechanisms of polycomb gene silencing: knowns and unknowns. Nat. Rev. Mol. Cell Biol. 10, 697-708.
  22. Simon, J. A. and C. A. Lange. 2008. Roles of the EZH2 histone methyltransferase in cancer epigenetics. Mutat. Res. 647, 21-29. https://doi.org/10.1016/j.mrfmmm.2008.07.010
  23. Tachibana, M., K. Sugimoto, T. Fukushima, and Y. Shinkai. 2001. Set domain-containing protein, G9a, is a novel lysine-preferring mammalian histone methyltransferase with hyperactivity and specific selectivity to lysines 9 and 27 of histone H3. J. Biol. Chem. 276, 25309-25317. https://doi.org/10.1074/jbc.M101914200
  24. Tie, F., R. Banerjee, C. A. Stratton, J. Prasad-Sinha, V. Stepanik, A. Zlobin, M. O. Diaz, P. C. Scacheri, and P. J. Harte. 2009. CBP-mediated acetylation of histone H3 lysine 27 antagonizes Drosophila Polycomb silencing. Development 136, 3131-3141. https://doi.org/10.1242/dev.037127
  25. Vakoc, C. R., M. M. Sachdeva, H. Wang, and G. A. Blobel. 2006. Profile of histone lysine methylation across transcribed mammalian chromatin. Mol. Cell Biol. 26, 9185-9195. https://doi.org/10.1128/MCB.01529-06
  26. Wang, Z., C. Zang, J. A. Rosenfeld, D. E. Schones, A. Barski, S. Cuddapah, K. Cui, T. Y. Roh, W. Peng, M. Q. Zhang, and K. Zhao. 2008. Combinatorial patterns of histone acetylations and methylations in the human genome. Nat. Genet. 40, 897-903. https://doi.org/10.1038/ng.154