組蛋白甲基化
組蛋白甲基化（Histone methylation）是真核生物染色體上包裹DNA的組蛋白之離胺酸或精胺酸被甲基化的轉譯後修飾，多發生在組蛋白H3與組蛋白H4向外延伸的N端尾[1]，此反應由组蛋白甲基转移酶（HMT）催化，將S-腺苷甲硫氨酸（SAM）中的甲基轉移到組蛋白上[2]，其中離胺酸可被加上一至三個甲基（取代NH3+基團上的氫離子），精胺酸則可被加上一或兩個甲基（取代NH2基團上的氫離子），過去認為此修飾不可逆，但現在已知有組蛋白脫甲基酶（HDM）可將組蛋白上的甲基水解移除[3]。組蛋白甲基化可影響染色體結構以及與其他蛋白的結合力，因被修飾的胺基酸種類和加上的甲基數目不同，此修飾可能促進或降低基因的轉錄，如H3K4me2、H3K4me3與H3K79me3一般可促進轉錄，H3K9me2、H3K9me3、H3K27me2、H3K27me3和H4K20me3則抑制轉錄[4]，另外有些組蛋白甲基化位點和DNA修復有關，可與參與DNA修復的蛋白結合[5]。組蛋白上不同位點的多種修飾（包括甲基化、乙醯化、磷酸化等）可能組合成組蛋白密碼，共同影響染色體結構，並與細胞中的其他蛋白結合以調控基因的轉錄[6][7]
雌性哺乳類細胞中X染色體去活化的過程中，去活化的X染色體（Xi）即受到H3K9me3、H3K27me3等位點的組蛋白甲基化，由與长链非编码RNAXist結合的多梳家族蛋白進行修飾，進而成為異染色質[8]。組蛋白甲基化的異常與數種癌症有關[9]。
参见
參考文獻
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- ^ 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
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- ^ 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.
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