組織蛋白甲基化

組織蛋白甲基化（Histone methylation）是真核生物染色體上包裹DNA的組織蛋白之離胺酸或精胺酸被甲基化的轉譯後修飾，多發生在組織蛋白H3（英語：Histone H3）與組織蛋白H4（英語：Histone H4）向外延伸的N端尾^[1]，此反應由組織蛋白甲基轉移酶（HMT）催化，將S-腺苷甲硫胺酸（SAM）中的甲基轉移到組織蛋白上^[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，但現在已知有組織蛋白脫甲基酶（英語：demethylase）（HDM）可將組織蛋白上的甲基水解移除^[3]。組織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（英語：H3K4me3）與H3K79me3一般可促進轉錄，H3K9me2（英語：H3K9me2）、H3K9me3（英語：H3K9me3）、H3K27me2、H3K27me3（英語：H3K27me3）和H4K20me3（英語：H4K20me3）則抑制轉錄^[4]，另外有些組織蛋白甲基化位點和DNA修復有關，可與參與DNA修復的蛋白結合^[5]。組織蛋白上不同位點的多種修飾（包括甲基化、乙醯化、磷酸化等）可能組合成組織蛋白密碼，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等位點的組織蛋白甲基化，由與長鏈非編碼RNAXist（英語：Xist）結合的多梳家族蛋白進行修飾，進而成為異染色質^[8]。組織蛋白甲基化的異常與數種癌症有關^[9]。

參見

參考文獻

^ Jia, Songtao; Wang, Yu. Degrees make all the difference (PDF). Epigenetics. 2009, 4 (5): 1–4 [2021-04-24]. （原始內容存檔 (PDF)於2011-03-01）.
^ Wood A. Posttranslational Modifications of Histones by Methylation. Conaway JW, Conaway RC (編). 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.

[1] Jia, Songtao; Wang, Yu. Degrees make all the difference (PDF). Epigenetics. 2009, 4 (5): 1–4 [2021-04-24]. （原始內容存檔 (PDF)於2011-03-01）.

[Posttranslational-2] Wood A. Posttranslational Modifications of Histones by Methylation. Conaway JW, Conaway RC (編). 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.

[3] 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.

[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.

[pmid29937925-5] 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

[pmid31747960-9] 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.

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