Chaperone control of the activity and specificity of the histone H3 acetyltransferase Rtt109
Chaperone control of the activity and specificity of the histone H3 acetyltransferase Rtt109
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DOI：
10.1128/mcb.00182-08
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发表时间：
2008-07-01
影响因子：
5.3
通讯作者：
Greenblatt, Jack F.
中科院分区：
文献类型：
--
作者：
Fillingham, Jeffrey;Recht, Judith;Greenblatt, Jack F.
组蛋白乙酰转移酶（HAT）Rtt 109对K56上的酿酒酵母组蛋白H3的乙酰化对于修复复制相关损伤是重要的。Rtt 109从酵母中纯化，与组蛋白伴侣Vps 75复合，其在体内稳定HAT。一个全基因组筛选，以确定基因的缺失与rtt 109三角洲合成遗传相互作用表明，Rtt 109有功能，除了DNA修复。我们表明，除了其已知的H3-K56乙酰化活性，Rtt 109也是一个H3-K9 HAT，我们表明，Rtt 109和Gcn 5是体内唯一的H3-K9 HAT。Vps 75强烈增强Rtt 109的体外H3-K9乙酰化活性。另一种组蛋白伴侣Asf 1和Vps 75都是Rtt 109在体内乙酰化H3（H3-K9 ac）上的赖氨酸9所需的，而H3-K56 ac在体内仅需要Asf 1。Asf 1还与核Hat 1/Hat 2/Hif 1复合物发生物理相互作用，使H4-K5和H4-K12乙酰化。我们认为Asf 1能够组装成染色质H3-H4二聚体，在H4-K5/12和H3-K9/56上双乙酰化。
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 rtt109 Delta 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.