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首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America >Histone H3 N-terminus regulates higher order structure of yeast heterochromatin
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Histone H3 N-terminus regulates higher order structure of yeast heterochromatin

机译:组蛋白H3 N端调节酵母异染色质的高阶结构

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In budding yeast, telomeres and the mating type (HM) loci are found in a heterochromatin-like silent structure initiated by Rap1 and extended by the interaction of Silencing Information Regulator (Sir) proteins with histones. Binding data demonstrate that both the H3 and H4 N-terminal domains required for silencing in vivo interact directly with Sir3 and Sir4 in vitro. The role of H4 lysine 16 deacetylation is well established in Sir3 protein recruitment; however, that of the H3 N-terminal tail has remained unclear. To characterize the role of H3 in silent chromatin formation and compare it to H4 we have generated comprehensive high resolution genome-wide binding maps of heterochromatin proteins. We found that H4 lysine 16 deacetylation is required for the recruitment and spreading of heterochromatin proteins at all telomeres and HM loci. In contrast, the H3 N terminus is required for neither recruitment nor spreading of Sir proteins. Instead, deletion of the H3 tail leads to increased accessibility within heterochromatin of an ectopic bacterial dam methylase and the decreased mobility of an HML heterochromatic fragment in sucrose gradients. These findings indicate an altered chromatin structure. We propose that Sir proteins recruited by the H4 tail then interact with the H3 tail to form a higher order silent chromatin structure.
机译:在发芽的酵母中,端粒和交配型(HM)基因座位于Rap1启动的异染色质样沉默结构中,并通过沉默信息调节剂(Sir)蛋白质与组蛋白的相互作用而扩展。结合数据表明,体内沉默所需的H3和H4 N末端结构域在体外均与Sir3和Sir4直接相互作用。 H4赖氨酸16脱乙酰作用在Sir3蛋白募集中已得到充分证实;但是,H3 N末端尾巴的末端仍不清楚。为了表征H3在沉默染色质形成中的作用并将其与H4进行比较,我们生成了杂色染色质蛋白的全面高分辨率的全基因组结合图。我们发现,H4赖氨酸16脱乙酰化是在所有端粒和HM基因座处募集和传播异染色质蛋白所必需的。相反,H3 N末端既不是Sir蛋白的募集也不是传播。取而代之的是,H3尾部的缺失导致异位细菌坝甲基化酶异染色质中的可及性增加,而HML异色片段在蔗糖梯度中的迁移率降低。这些发现表明染色质结构发生了改变。我们建议由H4尾部招募的Sir蛋白然后与H3尾部相互作用以形成更高阶的沉默染色质结构。

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