维基百科

组蛋白密码

组蛋白密码（Histone code）是一个描述真核生物藉修饰包裹DNA的组蛋白（主要是其N端尾）以调控基因表达的理论，和DNA甲基化共同组成表观遗传密码（英语：epigenetic code）[2] 。组蛋白上的修饰包括乙酰化、甲基化、磷酸化、泛素化、二磷酸腺苷核糖基化、GlcNAc糖基化（英语：GlcNAc）[3]、瓜氨酸化、脯氨酸异构化（英语：Proline isomerization in epigenetics）[4]与SUMO修饰（英语：SUMO protein）等[5]，这些修饰的组合可影响染色体结构以及与其他蛋白的结合力，提升或降低基因的转录。人类细胞中组蛋白修饰的种类复杂，其中某几种修饰可能倾向出现在同一个组蛋白上[6]。近年由于质谱法技术的发展而有更多修饰种类与位点被发现[7]，也有许多研究探讨加上或移除组蛋白修饰的多种酵素，以及可辨认这些修饰而与之结合的其他蛋白[8]。

已知的组蛋白修饰位点与种类[1]

种类

编辑
组蛋白修饰对基因转录的影响
修饰种类 组蛋白位点
H3K4 H3K9 H3K14 H3K27 H3K79 H3K36 H4K20 H2BK5 H2BK20
单甲基化 促进[9] 促进[10] 促进[10] 促进[10][11] 促进[10] 促进[10]
双甲基化 抑制[12] 抑制[12] 促进[11]
三甲基化 促进[13] 抑制[10] 抑制[10] 促进[11]
抑制[10] 		促进 抑制[12]
乙酰化 促进[14] 促进[13] 促进[13] 促进[15] 促进

参考文献

编辑
  1. ^ Rodríguez-Paredes M, Esteller M. Cancer epigenetics reaches mainstream oncology.. Nat Med. 2011, 17 (3): 330–9. PMID 21386836. doi:10.1038/nm.2305. 
  2. ^ Jenuwein T, Allis C. Translating the histone code. Science. 2001, 293 (5532): 1074–80. PMID 11498575. doi:10.1126/science.1063127. 
  3. ^ K, Sakabe; Z, Wang; Gw, Hart. Beta-N-acetylglucosamine (O-GlcNAc) Is Part of the Histone Code. Proceedings of the National Academy of Sciences of the United States of America. 2010-11-16, 107 (46): 19915–20. Bibcode:2010PNAS..10719915S. PMC 2993388  . PMID 21045127. doi:10.1073/pnas.1009023107. 
  4. ^ Nelson CJ, Santos-Rosa H, Kouzarides T. Proline isomerization of histone H3 regulates lysine methylation and gene expression. Cell. September 2006, 126 (5): 905–16. PMID 16959570. doi:10.1016/j.cell.2006.07.026. 
  5. ^ Nathan D, Ingvarsdottir K, Sterner DE, et al. Histone sumoylation is a negative regulator in Saccharomyces cerevisiae and shows dynamic interplay with positive-acting histone modifications. Genes Dev. April 2006, 20 (8): 966–76. PMC 1472304  . PMID 16598039. doi:10.1101/gad.1404206. 
  6. ^ Wang Z, Zang C, Rosenfeld JA, Schones DE, Barski A, Cuddapah S, et al. Combinatorial patterns of histone acetylations and methylations in the human genome.. Nat Genet. 2008, 40 (7): 897–903. PMC 2769248  . PMID 18552846. doi:10.1038/ng.154. 
  7. ^ Tan M, Luo H, Lee S, Jin F, Yang JS, Montellier E, et al. Identification of 67 histone marks and histone lysine crotonylation as a new type of histone modification.. Cell. 2011, 146 (6): 1016–28. PMC 3176443  . PMID 21925322. doi:10.1016/j.cell.2011.08.008. 
  8. ^ Wang M, Mok MW, Harper H, Lee WH, Min J, Knapp S, Oppermann U, Marsden B, Schapira M. Structural Genomics of Histone Tail Recognition. Bioinformatics. 24 Aug 2010, 26 (20): 2629–2630. PMC 2951094  . PMID 20739309. doi:10.1093/bioinformatics/btq491. 
  9. ^ Benevolenskaya EV. Histone H3K4 demethylases are essential in development and differentiation. Biochemistry and Cell Biology = Biochimie Et Biologie Cellulaire. August 2007, 85 (4): 435–43. PMID 17713579. doi:10.1139/o07-057. 
  10. ^ 10.0 10.1 10.2 10.3 10.4 10.5 10.6 10.7 Barski A, Cuddapah S, Cui K, Roh TY, Schones DE, Wang Z, et al. High-resolution profiling of histone methylations in the human genome. Cell. May 2007, 129 (4): 823–37. PMID 17512414. doi:10.1016/j.cell.2007.05.009. 
  11. ^ 11.0 11.1 11.2 Steger DJ, Lefterova MI, Ying L, Stonestrom AJ, Schupp M, Zhuo D, et al. DOT1L/KMT4 recruitment and H3K79 methylation are ubiquitously coupled with gene transcription in mammalian cells. Molecular and Cellular Biology. April 2008, 28 (8): 2825–39. PMC 2293113  . PMID 18285465. doi:10.1128/MCB.02076-07. 
  12. ^ 12.0 12.1 12.2 Rosenfeld JA, Wang Z, Schones DE, Zhao K, DeSalle R, Zhang MQ. Determination of enriched histone modifications in non-genic portions of the human genome. BMC Genomics. March 2009, 10: 143. PMC 2667539  . PMID 19335899. doi:10.1186/1471-2164-10-143. 
  13. ^ 13.0 13.1 13.2 Koch CM, Andrews RM, Flicek P, Dillon SC, Karaöz U, Clelland GK, et al. The landscape of histone modifications across 1% of the human genome in five human cell lines. Genome Research. June 2007, 17 (6): 691–707. PMC 1891331  . PMID 17567990. doi:10.1101/gr.5704207. 
  14. ^ Guillemette B, Drogaris P, Lin HH, Armstrong H, Hiragami-Hamada K, Imhof A, et al. H3 lysine 4 is acetylated at active gene promoters and is regulated by H3 lysine 4 methylation. PLoS Genetics. March 2011, 7 (3): e1001354. PMC 3069113  . PMID 21483810. doi:10.1371/journal.pgen.1001354. 
  15. ^ Creyghton MP, Cheng AW, Welstead GG, Kooistra T, Carey BW, Steine EJ, et al. Histone H3K27ac separates active from poised enhancers and predicts developmental state. Proceedings of the National Academy of Sciences of the United States of America. December 2010, 107 (50): 21931–6. PMC 3003124  . PMID 21106759. doi:10.1073/pnas.1016071107. 
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