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首页> 外文期刊>Molecular biology of the cell >HST3/HST4-dependent Deacetylation of Lysine 56 of Histone H3 in Silent Chromatin
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HST3/HST4-dependent Deacetylation of Lysine 56 of Histone H3 in Silent Chromatin

机译:HST3 / HST4依赖组蛋白H3在沉默染色质中赖氨酸56的脱乙酰作用

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The composition of posttranslational modifications on newly synthesized histones must be altered upon their incorporation into chromatin. These changes are necessary to maintain the same gene expression state at individual chromosomal loci before and after DNA replication. We have examined how one modification that occurs on newly synthesized histone H3, acetylation of K56, influences gene expression at epigenetically regulated loci in Saccharomyces cerevisiae. H3 K56 is acetylated by Rtt109p before its incorporation into chromatin during S phase, and this modification is then removed by the NAD(+)-dependent deacetylases Hst3p and Hst4p during G2/M phase. We found silenced loci maintain H3 K56 in a hypoacetylated state, and the absence of this modification in rtt109 mutants was compatible with HM and telomeric silencing. In contrast, loss of HST3 and HST4 resulted in hyperacetylation of H3 K56 within silent loci and telomeric silencing defects, despite the continued presence of Sir2p throughout these loci. These silencing defects in hst3 Delta hst4 Delta mutants could be suppressed by deletion of RTT109. In contrast, overexpression of Sir2p could not restore silencing in hst3 Delta hst4 Delta mutants. Together, our findings argue that HST3 HST4 play critical roles in maintaining the hypoacetylated state of K56 on histone H3 within silent chromatin.
机译:在新合成的组蛋白上掺入染色质后,必须改变其翻译后修饰的组成。这些变化对于在DNA复制之前和之后在单个染色体基因座上保持相同的基因表达状态是必需的。我们已经研究了在新合成的组蛋白H3上发生的一种修饰,即K56的乙酰化,如何影响酿酒酵母中表观遗传调控基因座上的基因表达。 H3 K56在S期被掺入染色质之前被Rtt109p乙酰化,然后在G2 / M期被NAD(+)依赖性脱乙酰基酶Hst3p和Hst4p去除这种修饰。我们发现沉默的基因座将H3 K56维持在低乙酰化状态,并且rtt109突变体中这种修饰的缺失与HM和端粒沉默兼容。相反,尽管Sir2p在这些基因座中持续存在,但HST3和HST4的缺失导致沉默基因座和端粒沉默缺陷内的H3 K56过度乙酰化。通过删除RTT109,可以抑制hst3 Delta hst4 Delta突变体中的这些沉默缺陷。相反,在hst3 Delta hst4 Delta突变体中,Sir2p的过表达不能恢复沉默。总之,我们的发现认为HST3 HST4在维持沉默染色质中组蛋白H3上K56的低乙酰化状态中起关键作用。

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