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组蛋白伴侣抗沉默功能1在S期刺激新合成的组蛋白H3的乙酰化。

The histone chaperone anti-silencing function 1 stimulates the acetylation of newly synthesized histone H3 in S-phase.

作者信息

Adkins Melissa W, Carson Joshua J, English Christine M, Ramey Christopher J, Tyler Jessica K

机构信息

Department of Biochemistry and Molecular Genetics, School of Medicine, University of Colorado, Aurora, Colorado 80045, USA.

出版信息

J Biol Chem. 2007 Jan 12;282(2):1334-40. doi: 10.1074/jbc.M608025200. Epub 2006 Nov 15.

Abstract

Anti-silencing function 1 (Asf1) is a highly conserved chaperone of histones H3/H4 that assembles or disassembles chromatin during transcription, replication, and repair. We have found that budding yeast lacking Asf1 has greatly reduced levels of histone H3 acetylated at lysine 9. Lysine 9 is acetylated on newly synthesized budding yeast histone H3 prior to its assembly onto newly replicated DNA. Accordingly, we found that the vast majority of H3 Lys-9 acetylation peaked in S-phase, and this S-phase peak of H3 lysine 9 acetylation was absent in yeast lacking Asf1. By contrast, deletion of ASF1 has no effect on the S-phase specific peak of H4 lysine 12 acetylation; another modification carried by newly synthesized histones prior to chromatin assembly. We show that Gcn5 is the histone acetyltransferase responsible for the S-phase-specific peak of H3 lysine 9 acetylation. Strikingly, overexpression of Asf1 leads to greatly increased levels of H3 on acetylation on lysine 56 and Gcn5-dependent acetylation on lysine 9. Analysis of a panel of Asf1 mutations that modulate the ability of Asf1 to bind to histones H3/H4 demonstrates that the histone binding activity of Asf1 is required for the acetylation of Lys-9 and Lys-56 on newly synthesized H3. These results demonstrate that Asf1 does not affect the stability of the newly synthesized histones per se, but instead histone binding by Asf1 promotes the efficient acetylation of specific residues of newly synthesized histone H3.

摘要

抗沉默功能1(Asf1)是组蛋白H3/H4的一种高度保守的伴侣蛋白,在转录、复制和修复过程中组装或拆卸染色质。我们发现,缺乏Asf1的芽殖酵母中,赖氨酸9位乙酰化的组蛋白H3水平大幅降低。在新合成的芽殖酵母组蛋白H3组装到新复制的DNA上之前,赖氨酸9位会发生乙酰化。因此,我们发现绝大多数H3赖氨酸9位乙酰化在S期达到峰值,而在缺乏Asf1的酵母中不存在这种H3赖氨酸9位乙酰化的S期峰值。相比之下,缺失ASF1对H4赖氨酸12位乙酰化的S期特异性峰值没有影响;这是新合成组蛋白在染色质组装之前发生的另一种修饰。我们表明,Gcn5是负责H3赖氨酸9位乙酰化S期特异性峰值的组蛋白乙酰转移酶。引人注目的是,Asf1的过表达导致赖氨酸56位乙酰化的H3水平大幅增加以及赖氨酸9位的Gcn5依赖性乙酰化增加。对一组调节Asf1与组蛋白H3/H4结合能力的Asf1突变体的分析表明,Asf1的组蛋白结合活性是新合成H3上赖氨酸9位和赖氨酸56位乙酰化所必需的。这些结果表明,Asf1本身并不影响新合成组蛋白的稳定性,而是Asf1与组蛋白的结合促进了新合成组蛋白H3特定残基的有效乙酰化。

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