伴侣蛋白对组蛋白H3乙酰转移酶Rtt109活性和特异性的调控

Chaperone control of the activity and specificity of the histone H3 acetyltransferase Rtt109.

作者信息

Fillingham Jeffrey, Recht Judith, Silva Andrea C, Suter Bernhard, Emili Andrew, Stagljar Igor, Krogan Nevan J, Allis C David, Keogh Michael-Christopher, Greenblatt Jack F

机构信息

Banting and Best Department of Medical Research, Terrence Donnelly Centre for Cellular and Biomolecular Research (CCBR), University of Toronto, 160 College St., Toronto, Ontario M5S 3E1, Canada.

出版信息

Mol Cell Biol. 2008 Jul;28(13):4342-53. doi: 10.1128/MCB.00182-08. Epub 2008 May 5.

Abstract

Acetylation of Saccharomyces cerevisiae histone H3 on K56 by the histone acetyltransferase (HAT) Rtt109 is important for repairing replication-associated lesions. Rtt109 purifies from yeast in complex with the histone chaperone Vps75, which stabilizes the HAT in vivo. A whole-genome screen to identify genes whose deletions have synthetic genetic interactions with rtt109Delta suggests Rtt109 has functions in addition to DNA repair. We show that in addition to its known H3-K56 acetylation activity, Rtt109 is also an H3-K9 HAT, and we show that Rtt109 and Gcn5 are the only H3-K9 HATs in vivo. Rtt109's H3-K9 acetylation activity in vitro is enhanced strongly by Vps75. Another histone chaperone, Asf1, and Vps75 are both required for acetylation of lysine 9 on H3 (H3-K9ac) in vivo by Rtt109, whereas H3-K56ac in vivo requires only Asf1. Asf1 also physically interacts with the nuclear Hat1/Hat2/Hif1 complex that acetylates H4-K5 and H4-K12. We suggest Asf1 is capable of assembling into chromatin H3-H4 dimers diacetylated on both H4-K5/12 and H3-K9/56.

摘要

组蛋白乙酰转移酶(HAT)Rtt109对酿酒酵母组蛋白H3的K56位点进行乙酰化修饰,这对于修复复制相关损伤至关重要。Rtt109在酵母中与组蛋白伴侣Vps75结合纯化,Vps75在体内可稳定该HAT。一项全基因组筛选旨在鉴定其缺失与rtt109Δ具有合成遗传相互作用的基因,结果表明Rtt109除了具有DNA修复功能外还有其他功能。我们发现,除了已知的H3-K56乙酰化活性外,Rtt109还是一种H3-K9 HAT,并且我们证明Rtt109和Gcn5是体内仅有的H3-K9 HAT。Vps75可强烈增强Rtt109在体外的H3-K9乙酰化活性。另一种组蛋白伴侣Asf1以及Vps75都是Rtt109在体内对H3赖氨酸9位点(H3-K9ac)进行乙酰化所必需的,而H3-K56ac在体内仅需要Asf1。Asf1还与使H4-K5和H4-K12乙酰化的核Hat1/Hat2/Hif1复合物发生物理相互作用。我们认为Asf1能够组装成在H4-K5/12和H3-K9/56上均发生双乙酰化的染色质H3-H4二聚体。

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