组蛋白八聚体结构在 ISW2 ATP 依赖性核小体重塑的早期发生改变。

Histone Octamer Structure Is Altered Early in ISW2 ATP-Dependent Nucleosome Remodeling.

机构信息

Department of Epigenetics and Molecular Carcinogenesis, University of Texas MD Anderson Cancer Center - Science Park, Smithville, TX 78957, USA; Catalent Pharma Solutions, 726 Heartland Trail, Madison, WI 53717, USA.

Department of Epigenetics and Molecular Carcinogenesis, University of Texas MD Anderson Cancer Center - Science Park, Smithville, TX 78957, USA.

出版信息

Cell Rep. 2019 Jul 2;28(1):282-294.e6. doi: 10.1016/j.celrep.2019.05.106.

DOI:10.1016/j.celrep.2019.05.106

PMID:31269447

Abstract

Nucleosomes are the fundamental building blocks of chromatin that regulate DNA access and are composed of histone octamers. ATP-dependent chromatin remodelers like ISW2 regulate chromatin access by translationally moving nucleosomes to different DNA regions. We find that histone octamers are more pliable than previously assumed and distorted by ISW2 early in remodeling before DNA enters nucleosomes and the ATPase motor moves processively on nucleosomal DNA. Uncoupling the ATPase activity of ISW2 from nucleosome movement with deletion of the SANT domain from the C terminus of the Isw2 catalytic subunit traps remodeling intermediates in which the histone octamer structure is changed. We find restricting histone movement by chemical crosslinking also traps remodeling intermediates resembling those seen early in ISW2 remodeling with loss of the SANT domain. Other evidence shows histone octamers are intrinsically prone to changing their conformation and can be distorted merely by H3-H4 tetramer disulfide crosslinking.

摘要

核小体是染色质的基本组成单位，可调节 DNA 的可及性，由组蛋白八聚体组成。ATP 依赖的染色质重塑酶（如 ISW2）通过将核小体平移到不同的 DNA 区域来调节染色质的可及性。我们发现组蛋白八聚体比之前认为的更具柔韧性，并且在 DNA 进入核小体之前，ISW2 会早期对其进行扭曲，然后 ATP 酶马达在核小体 DNA 上进行连续运动。通过从 Isw2 催化亚基的 C 末端删除 SANT 结构域，将 ISW2 的 ATP 酶活性与核小体运动解耦，会捕获到重塑中间体，其中组蛋白八聚体结构发生改变。我们发现通过化学交联限制组蛋白运动也会捕获到类似于缺失 SANT 结构域的 ISW2 重塑早期所看到的重塑中间体。其他证据表明组蛋白八聚体本身就容易改变其构象，并且仅通过 H3-H4 四聚体二硫键交联就可以使其发生扭曲。