小柯机器人

HP1蛋白促进异染色质相分离
2019-10-17 14:03

美国加州大学旧金山分校G. J. Narlikar和J. D. Gross等研究人员合作发现HP1蛋白重塑核小体核心,从而促进异染色质相分离。2019年10月16日,国际知名学术期刊《自然》在线发表了这一成果。

研究人员发现由裂殖酵母HP1蛋白Swi6产生的染色质紧缩会导致相分离的液体浓缩物。值得注意的是,研究人员进一步发现Swi6大大增加了核小体中掩盖组蛋白残基的可及性和动态。限制这些动态会损害Swi6染色质在液滴中的紧实度。这些结果表明,Swi6通过一个反常机制(即动态暴露掩盖的核小体区域)将寡聚化与染色质的相分离联系在一起。

研究人员认为,通过Swi6对八聚体核心的这种重塑增加了核小体之间多价相互作用的机会,从而促进了相分离。这种机制可能更普遍地驱动染色质组织,而不仅仅是异染色质。

据悉,异染色质在多个尺度上影响基因组功能。它能够实现可遗传的基因抑制,维持染色体完整性并为细胞核提供机械刚度。已经提出这些多样化的功能一定程度上由染色质的压缩引起。主要类型的异染色质在其核心处包含HP1蛋白与染色质之间形成的复合物,该复合物在组蛋白H3赖氨酸9(H3K9me)上被甲基化。HP1被认为利用寡聚来将染色质压紧成相分离的浓缩物。目前,尚不清楚HP1介导的相分离与染色质压缩的关系。

附:英文原文

Title: HP1 reshapes nucleosome core to promote heterochromatin phase separation

Author: S. Sanulli, M. J. Trnka, V. Dharmarajan, R. W. Tibble, B. D. Pascal, A. L. Burlingame, P. R. Griffin, J. D. Gross, G. J. Narlikar

Issue&Volume: 2019-10-16

Abstract: 

Heterochromatin impacts genome function at multiple scales. It enables heritable gene repression, maintains chromosome integrity and provides mechanical rigidity to the nucleus1,2. It has been proposed that these diverse functions arise in part from compaction of the underlying chromatin. A major type of heterochromatin contains at its core the complex formed between HP1 proteins and chromatin that is methylated on histone H3, lysine 9 (H3K9me). HP1 is proposed to use oligomerization to compact chromatin into phase-separated condensates3–6. Yet how HP1-mediated phase separation relates to chromatin compaction remains unclear. Here we demonstrate that chromatin compaction by the S. pombe HP1 protein, Swi6, results in phase-separated liquid condensates. Remarkably, we further find that Swi6 substantially increases the accessibility and dynamics of buried histone residues within a nucleosome. Restraining these dynamics impairs chromatin compaction by Swi6 into liquid droplets. Our results indicate that Swi6 couples oligomerization to the phase separation of chromatin by a counter-intuitive mechanism, namely dynamic exposure of buried nucleosomal regions. We propose that such reshaping of the octamer core by Swi6 increases opportunities for multivalent interactions between nucleosomes, thereby promoting phase separation. This mechanism may more generally drive chromatin organization beyond heterochromatin.

DOI: 10.1038/s41586-019-1669-2

Source:https://www.nature.com/articles/s41586-019-1669-2

Nature:《自然》,创刊于1869年。隶属于施普林格·自然出版集团,最新IF:43.07
官方网址:http://www.nature.com/
投稿链接:http://www.nature.com/authors/submit_manuscript.html


本期文章:《自然》:Online/在线发表

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