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的组蛋白之赖氨酸或精氨酸被甲基化的翻译后修饰，多发生在组蛋白H3与组蛋白H4向外延伸的N端尾[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（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H3K4me2、H3K4me3与H3K79me3一般可促进转录，H3K9me2、H3K9me3、H3K27me2、H3K27me3和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]
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]。
参见
[编辑]
参考文献
[编辑]- ^ Jia, Songtao; Wang, Yu. Degrees make all the difference (PDF). Epigenetics. 2009, 4 (5): 1–4 [2021-04-24]. （原始内容存档 (PDF)于2011-03-01）.
- ^ 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.
- ^ Klose RJ, Zhang Y. Regulation of histone methylation by demethylimination and demethylation. Nature Reviews Molecular Cell Biology. Apr 2007, 8 (4): 307–18. PMID 17342184. doi:10.1038/nrm2143.
- ^ 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.
- ^ 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.
- ^ 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.
- ^ 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.
- ^ 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
- ^ 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.
