组蛋白甲基化

组蛋白甲基化(Histone methylation)是真核生物染色体上包裹DNA组蛋白赖氨酸精氨酸甲基化翻译后修饰,多发生在组蛋白H3英语Histone H3组蛋白H4英语Histone H4向外延伸的N端[1],此反应由组蛋白甲基转移酶(HMT)催化,将S-腺苷甲硫氨酸(SAM)中的甲基转移到组蛋白上[2],其中赖氨酸可被加上一至三个甲基(取代NH3+基团上的氢离子),精氨酸则可被加上一或两个甲基(取代NH2基团上的氢离子),过去认为此修饰不可逆,但现在已知有组蛋白脱甲基酶英语demethylase(HDM)可将组蛋白上的甲基水解移除[3]。组蛋白甲基化可影响染色体结构以及与其他蛋白的结合力,因被修饰的氨基酸种类和加上的甲基数目不同,此修饰可能促进或降低基因的转录,如H3K4me2H3K4me3英语H3K4me3H3K79me3一般可促进转录,H3K9me2英语H3K9me2H3K9me3英语H3K9me3H3K27me2H3K27me3英语H3K27me3H4K20me3英语H4K20me3则抑制转录[4],另外有些组蛋白甲基化位点和DNA修复有关,可与参与DNA修复的蛋白结合[5]。组蛋白上不同位点的多种修饰(包括甲基化、乙酰化磷酸化等)可能组合成组蛋白密码,共同影响染色体结构,并与细胞中的其他蛋白结合以调控基因的转录[6][7]

组蛋白甲基转移酶

雌性哺乳类细胞中X染色体去激活的过程中,去激活的X染色体(Xi)即受到H3K9me3、H3K27me3等位点的组蛋白甲基化,由与长链非编码RNAXist英语Xist结合的多梳家族蛋白进行修饰,进而成为异染色质[8]。组蛋白甲基化的异常与数种癌症有关[9]

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参考文献

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  2. ^ Wood A. Posttranslational Modifications of Histones by Methylation. Conaway JW, Conaway RC (编). Proteins in eukaryotic transcription. Advances in Protein Chemistry 67. Amsterdam: Elsevier Academic Press. 2004: 201–222. ISBN 0-12-034267-7. PMID 14969729. doi:10.1016/S0065-3233(04)67008-2. 
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  4. ^ Kooistra, Susanne Marije; Helin, Kristian. Molecular mechanisms and potential functions of histone demethylases. Nature Reviews Molecular Cell Biology. 2012-04-04, 13 (5): 297–311. ISSN 1471-0072. PMID 22473470. doi:10.1038/nrm3327. 
  5. ^ Wei S, Li C, Yin Z, Wen J, Meng H, Xue L, Wang J. Histone methylation in DNA repair and clinical practice: new findings during the past 5-years. J Cancer. 2018, 9 (12): 2072–2081. PMC 6010677 . PMID 29937925. doi:10.7150/jca.23427. 
  6. ^ Chi P, Allis CD, Wang GG. Covalent histone modifications--miswritten, misinterpreted and mis-erased in human cancers. Nature Reviews. Cancer. July 2010, 10 (7): 457–69. PMC 3262678 . PMID 20574448. doi:10.1038/nrc2876. 
  7. ^ Barratt MJ, Hazzalin CA, Cano E, Mahadevan LC. Mitogen-stimulated phosphorylation of histone H3 is targeted to a small hyperacetylation-sensitive fraction. Proceedings of the National Academy of Sciences of the United States of America. May 1994, 91 (11): 4781–5. Bibcode:1994PNAS...91.4781B. PMC 43872 . PMID 8197135. doi:10.1073/pnas.91.11.4781. 
  8. ^ Ng K, Pullirsch D, Leeb M, Wutz A. Xist and the order of silencing. EMBO Reports. January 2007, 8 (1): 34–9. PMC 1796754 . PMID 17203100. doi:10.1038/sj.embor.7400871. Table 1 Features of the inactive X territory 
  9. ^ Zhao Z, Shilatifard A. Epigenetic modifications of histones in cancer.. Genome Biol. 2019, 20 (1): 245. PMC 6868810 . PMID 31747960. doi:10.1186/s13059-019-1870-5.