組蛋白甲基化 - 维基百科,自由的百科全书
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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
[编辑]參考文獻
[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
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- ^ 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
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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
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