組蛋白乙酰化
外觀
組蛋白乙酰化(Histone acetylation)為真核生物染色體上包裹DNA的組蛋白N端之離胺酸被乙酰化的轉譯後修飾,為細胞調控基因表達的一種機制。此反應一般由組蛋白乙酰轉移酶(HAT)催化,組蛋白脫乙酰酶(HDAC)則可催化其逆反應組蛋白脫乙酰化( Histone deacetylation),將組蛋白上的乙酰基水解移除[1]。組蛋白乙酰化是為一種表觀遺傳修飾,乙酰基化會消除組蛋白離胺酸所帶的正電荷,使其與DNA(帶負電)的結合力降低[2],因此可將原本纏繞較緊密的染色體結構(異染色質)轉成較疏鬆的型態(真染色質),有利於轉錄的進行而提升基因表達;組蛋白脫乙酰化的功能則與之相反,可使染色體結構變得更緊密而降低基因表達[3][4]。
組蛋白上不同位點的多種修飾(包括乙酰化、甲基化、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[5][6],例如具有布羅莫結構域的蛋白(包括許多轉錄因子)可與被乙酰化的組蛋白結合[7] 。組蛋白密碼與DNA甲基化皆為表觀遺傳密碼的一部份[8]。
組蛋白乙酰化調控許多基因的表現,因此其調控異常與發炎性疾病、心血管疾病、神經性疾病和多種癌症相關[9][10]。此外對煙酒和藥物的成癮機制可能也與其促進染色體特定區域的組蛋白乙酰化以影響基因表達有關[11][12]。
參考文獻
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- ^ Barnes PJ, Adcock IM, Ito K. Histone acetylation and deacetylation: importance in inflammatory lung diseases. The European Respiratory Journal. March 2005, 25 (3): 552–63. PMID 15738302. doi:10.1183/09031936.05.00117504.
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