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HP1 和 Brg1/Brm 与组蛋白 H3 球形结构域的相互作用是 HP1 介导的抑制所必需的。

Interaction of HP1 and Brg1/Brm with the globular domain of histone H3 is required for HP1-mediated repression.

机构信息

Institut Pasteur, Département de Biologie du Développement, Unité de Recherche Associée URA2578 du Centre National de la Recherche Scientifique CNRS, Unité de Régulation Epigénétique, équipe AVENIR de l'Institut National de la Santé Et de la Recherche Médicale INSERM, Paris, France.

出版信息

PLoS Genet. 2009 Dec;5(12):e1000769. doi: 10.1371/journal.pgen.1000769. Epub 2009 Dec 11.

Abstract

The heterochromatin-enriched HP1 proteins play a critical role in regulation of transcription. These proteins contain two related domains known as the chromo- and the chromoshadow-domain. The chromo-domain binds histone H3 tails methylated on lysine 9. However, in vivo and in vitro experiments have shown that the affinity of HP1 proteins to native methylated chromatin is relatively poor and that the opening of chromatin occurring during DNA replication facilitates their binding to nucleosomes. These observations prompted us to investigate whether HP1 proteins have additional histone binding activities, envisioning also affinity for regions potentially occluded by the nucleosome structure. We find that the chromoshadow-domain interacts with histone H3 in a region located partially inside the nucleosomal barrel at the entry/exit point of the nucleosome. Interestingly, this region is also contacted by the catalytic subunits of the human SWI/SNF complex. In vitro, efficient SWI/SNF remodeling requires this contact and is inhibited in the presence of HP1 proteins. The antagonism between SWI/SNF and HP1 proteins is also observed in vivo on a series of interferon-regulated genes. Finally, we show that SWI/SNF activity favors loading of HP1 proteins to chromatin both in vivo and in vitro. Altogether, our data suggest that HP1 chromoshadow-domains can benefit from the opening of nucleosomal structures to bind chromatin and that HP1 proteins use this property to detect and arrest unwanted chromatin remodeling.

摘要

富含异染色质的 HP1 蛋白在转录调控中起着关键作用。这些蛋白质包含两个相关的结构域,分别称为 chromo- 和 chromoshadow- 结构域。chromo 结构域结合组蛋白 H3 尾部赖氨酸 9 上的甲基化。然而,体内和体外实验表明,HP1 蛋白与天然甲基化染色质的亲和力相对较差,并且在 DNA 复制过程中发生的染色质开放有助于它们与核小体结合。这些观察结果促使我们研究 HP1 蛋白是否具有其他组蛋白结合活性,同时设想对潜在被核小体结构封闭的区域具有亲和力。我们发现 chromoshadow 结构域与核小体桶内部分位于核小体进入/退出点的组蛋白 H3 相互作用。有趣的是,该区域还与人类 SWI/SNF 复合物的催化亚基接触。在体外,有效的 SWI/SNF 重塑需要这种接触,并且在存在 HP1 蛋白的情况下受到抑制。SWI/SNF 和 HP1 蛋白之间的拮抗作用也在一系列干扰素调节基因中观察到。最后,我们表明 SWI/SNF 活性有利于 HP1 蛋白在体内和体外加载到染色质上。总之,我们的数据表明,HP1 chromoshadow 结构域可以从核小体结构的打开中受益,以结合染色质,并且 HP1 蛋白利用这种特性来检测和阻止不需要的染色质重塑。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/00ef/2782133/77d745f6e06d/pgen.1000769.g001.jpg

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