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組蛋白離胺酸精胺酸甲基化轉譯後修飾,多發生在組蛋白H3英语Histone H3組蛋白H4英语Histone H4向外延伸的N端[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英语demethylase(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H3K4me2H3K4me3英语H3K4me3H3K79me3一般可促進轉錄,H3K9me2英语H3K9me2H3K9me3英语H3K9me3H3K27me2H3K27me3英语H3K27me3H4K20me3英语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]

组蛋白甲基转移酶

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英语Xist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]

參考文獻编辑

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  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. 
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  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. 
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