組蛋白乙醯轉移酶

組蛋白乙醯轉移酶
組蛋白乙醯轉移酶MYST1的結構
识别码
EC編號 2.3.1.48
CAS号 9054-51-7
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基因本体 AmiGO / EGO

組蛋白乙醯轉移酶（Histone acetyltransferase，簡稱HAT）是真核生物細胞中將組蛋白乙醯化的酵素，此類酵素將乙醯輔酶A上的乙醯基轉移至組蛋白N端尾的離氨酸上，組蛋白乙醯化可降低其正電荷，使染色體的結構變疏鬆，促進其他蛋白（如具有布羅莫結構域的轉錄因子）與染色體結合，促進基因的轉錄[1]。

組蛋白乙醯轉移酶可依在細胞中的位置分為A型與B型兩大類[2]，其中大多數為前者，位於細胞核中，可將染色體（核小體）上的組蛋白乙醯化以促進基因表現[3]；後者則位於細胞質中，種類很少，代表者如HAT1（英语：HAT1）（但較新的研究結果認為HAT1可能也存在細胞核中，甚至可能比細胞質的部分多[4]），可將新轉譯產生、尚未組裝成核小體的組蛋白乙醯化，這些組蛋白進入細胞核組裝成核小體後，在細胞質中加上的乙醯基一般會被組蛋白脫乙醯酶移除[5]。組蛋白乙醯轉移酶還可依序列分為GNAT（Gcn5（英语：Gcn5）關聯N-乙醯轉移酶；Gcn5-related N-acetyltransferases）、MYST、p300/CBP等基因家族，此外核受體輔活化子（英语：Nuclear receptor coactivator 1）[6]、Rtt109[7]、TFIIIC和CLOCK（英语：CLOCK）等蛋白也都有組蛋白乙醯轉移酶的功能[8]。GNAT家族包括Gcn5、HAT1、ELP3（英语：ELP3）、ATF2（英语：Activating transcription factor 2）等，皆具有布羅莫結構域，可與已被乙醯化的組蛋白結合[2]；MYST家族包括MOZ（英语：KAT6A）、Ybf2、Sas2、Tip60（英语：KAT5）（得名自此四種蛋白名稱的縮寫）、KAT8（英语：KAT8）、KAT6B（英语：KAT6B）、KAT7（英语：KAT7 (gene)）等，其中許多具有鋅指與克羅莫結構域[9]。

組蛋白乙醯化的反應機理因轉移酶的種類不同而異，GNAT家族的轉移酶會同時與乙醯輔酶A和組蛋白結合，形成三元複合體（英语：ternary complex）[7]，MYST家族的轉移酶則是使用乒乓機制（Ping–pong mechanisms），先得到乙醯基再將其轉移到組蛋白上[10]。Gcn5與Rtt109等轉移酶需其他蛋白的輔助才能將組蛋白乙醯化[6][7]，有些需與其他蛋白組成複合體以提升組蛋白乙醯化的效率，如SAGA複合體與NuA4複合體（英语：NuA4 histone acetyltransferase complex）[6][11]。許多疾病與組蛋白乙醯轉移酶的調控異常有關[12][13]。

參考文獻

  1. ^ Sanchez R, Zhou MM. The role of human bromodomains in chromatin biology and gene transcription. Current Opinion in Drug Discovery & Development. September 2009, 12 (5): 659–65. PMC 2921942 可免费查阅. PMID 19736624. 
  2. ^ 2.0 2.1 Lee KK, Workman JL. Histone acetyltransferase complexes: one size doesn't fit all. Nature Reviews. Molecular Cell Biology. April 2007, 8 (4): 284–95. PMID 17380162. doi:10.1038/nrm2145. 
  3. ^ Weaver R. Molecular Biology. McGraw-Hill. 2007. ISBN 978-0073319940. 
  4. ^ Dutnall RN, Tafrov ST, Sternglanz R, Ramakrishnan V. Structure of the histone acetyltransferase Hat1: a paradigm for the GCN5-related N-acetyltransferase superfamily.. Cell. 1998, 94 (4): 427–38. PMID 9727486. doi:10.1016/s0092-8674(00)81584-6. 
  5. ^ Parthun MR. Hat1: the emerging cellular roles of a type B histone acetyltransferase.. Oncogene. 2007, 26 (37): 5319–28. PMID 17694075. doi:10.1038/sj.onc.1210602. 
  6. ^ 6.0 6.1 6.2 Sterner DE, Berger SL. Acetylation of histones and transcription-related factors. Microbiology and Molecular Biology Reviews. June 2000, 64 (2): 435–59. PMC 98999 可免费查阅. PMID 10839822. doi:10.1128/MMBR.64.2.435-459.2000. 
  7. ^ 7.0 7.1 7.2 Yuan H, Marmorstein R. Histone acetyltransferases: Rising ancient counterparts to protein kinases. Biopolymers. February 2013, 99 (2): 98–111. PMC 4017165 可免费查阅. PMID 23175385. doi:10.1002/bip.22128. 
  8. ^ Doi M, Hirayama J, Sassone-Corsi P. Circadian regulator CLOCK is a histone acetyltransferase. Cell. May 2006, 125 (3): 497–508. PMID 16678094. doi:10.1016/j.cell.2006.03.033. 
  9. ^ Roth SY, Denu JM, Allis CD. Histone acetyltransferases. Annual Review of Biochemistry. 2001, 70: 81–120. PMID 11395403. doi:10.1146/annurev.biochem.70.1.81. 
  10. ^ Berndsen CE, Albaugh BN, Tan S, Denu JM. Catalytic mechanism of a MYST family histone acetyltransferase. Biochemistry. January 2007, 46 (3): 623–9. PMC 2752042 可免费查阅. PMID 17223684. doi:10.1021/bi602513x. 
  11. ^ Kimura A, Matsubara K, Horikoshi M. A decade of histone acetylation: marking eukaryotic chromosomes with specific codes. Journal of Biochemistry. December 2005, 138 (6): 647–62. PMID 16428293. doi:10.1093/jb/mvi184. 
  12. ^ Cvetanovic M, Kular RK, Opal P. LANP mediates neuritic pathology in Spinocerebellar ataxia type 1. Neurobiol. Dis. December 2012, 48 (3): 526–32. PMC 3987943 可免费查阅. PMID 22884877. doi:10.1016/j.nbd.2012.07.024. 
  13. ^ Klein G, Vande Woude GF. Advances in Cancer Research, Volume 86. Boston: Academic Press. 2002. ISBN 978-0-12-006686-5. 

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