The histone chaperone anti-silencing function 1 stimulates the acetylation of newly synthesized histone H3 in S-phase
The histone chaperone anti-silencing function 1 stimulates the acetylation of newly synthesized histone H3 in S-phase
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DOI：
10.1074/jbc.m608025200
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发表时间：
2007-01-12
影响因子：
4.8
通讯作者：
Tyler, Jessica K.
中科院分区：
文献类型：
--
作者：
Adkins, Melissa W.;Carson, Joshua J.;Tyler, Jessica K.
抗沉默功能1 （Asf1）是组蛋白H3/H4的一个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的出芽酵母大大降低了赖氨酸9乙酰化的组蛋白H3水平。赖氨酸9在新合成的出芽酵母组蛋白H3上乙酰化，然后组装到新复制的DNA上。因此，我们发现绝大多数H3赖氨酸-9乙酰化峰出现在s期，而在缺乏Asf1的酵母中不存在H3赖氨酸-9乙酰化的s期峰。相比之下，ASF1的缺失对H4赖氨酸12乙酰化的s期特异性峰没有影响；在染色质组装之前，新合成的组蛋白携带的另一种修饰。我们发现Gcn5是负责H3赖氨酸9乙酰化s期特异性峰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乙酰化上的H3和赖氨酸9乙酰化上的gcn5依赖性水平显著升高。对一组调节Asf1与组蛋白H3/H4结合能力的Asf1突变的分析表明，Asf1的组蛋白结合活性是新合成的H3上Lys-9和Lys-56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，相反，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。
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.