染色质信号不同程度地决定了mSWI/SNF家族复合物的活性
2021-07-19   阅读:455   来源:科学

美国哈佛医学院Cigall Kadoch研究组发现,染色质信号不同程度地决定了mSWI/SNF家族复合物的活性。2021年7月16日出版的《科学》杂志发表了这项成果。

研究人员将内源性纯化的哺乳动物SWI/SNF(mSWI/SNF)复合物及其组装模块与不同的DNA编码单核体库进行对比,进行了25000多次结合和重塑测量。研究人员定义了组蛋白修饰、变体和突变对mSWI/SNF活性和染色质相互作用的单独和组合的特定影响。此外,研究人员确定了复合体模块组件、阅读结构域和核小体结合特性对复合体定位到特定染色质状态的组合贡献。这些发现揭示了一个主要染色质重塑复合物家族如何改变基因组的结合和活性。

据介绍,三磷酸腺苷依赖的染色质重塑因子mSWI/SNF调节基因组结构和基因表达,并在疾病中经常发生突变。然而,支配其核小体结合和重塑活动的具体染色质特征仍然是未知的。

附:英文原文

Title: Chromatin landscape signals differentially dictate the activities of mSWI/SNF family complexes

Author: Nazar Mashtalir, Hai T. Dao, Akshay Sankar, Hengyuan Liu, Aaron J. Corin, John D. Bagert, Eva J. Ge, Andrew R. D’Avino, Martin Filipovski, Brittany C. Michel, Geoffrey P. Dann, Tom W. Muir, Cigall Kadoch

Issue&Volume: 2021/07/16

Abstract: Mammalian SWI/SNF (mSWI/SNF) adenosine triphosphate–dependent chromatin remodelers modulate genomic architecture and gene expression and are frequently mutated in disease. However, the specific chromatin features that govern their nucleosome binding and remodeling activities remain unknown. We subjected endogenously purified mSWI/SNF complexes and their constituent assembly modules to a diverse library of DNA-barcoded mononucleosomes, performing more than 25,000 binding and remodeling measurements. Here, we define histone modification-, variant-, and mutation-specific effects, alone and in combination, on mSWI/SNF activities and chromatin interactions. Further, we identify the combinatorial contributions of complex module components, reader domains, and nucleosome engagement properties to the localization of complexes to selectively permissive chromatin states. These findings uncover principles that shape the genomic binding and activity of a major chromatin remodeler complex family.

DOI: 10.1126/science.abf8705

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