组蛋白八聚体核心的扭曲促进染色质重塑因子介导的核小体移动。
Distortion of histone octamer core promotes nucleosome mobilization by a chromatin remodeler.
作者信息
Sinha Kalyan K, Gross John D, Narlikar Geeta J
机构信息
Department of Biochemistry and Biophysics, University of California San Francisco, San Francisco, CA 94158, USA.
Department of Pharmaceutical Chemistry, University of California San Francisco, San Francisco, CA 94158, USA.
出版信息
Science. 2017 Jan 20;355(6322). doi: 10.1126/science.aaa3761.
Adenosine 5'-triphosphate (ATP)-dependent chromatin remodeling enzymes play essential biological roles by mobilizing nucleosomal DNA. Yet, how DNA is mobilized despite the steric constraints placed by the histone octamer remains unknown. Using methyl transverse relaxation-optimized nuclear magnetic resonance spectroscopy on a 450-kilodalton complex, we show that the chromatin remodeler, SNF2h, distorts the histone octamer. Binding of SNF2h in an activated ATP state changes the dynamics of buried histone residues. Preventing octamer distortion by site-specific disulfide linkages inhibits nucleosome sliding by SNF2h while promoting octamer eviction by the SWI-SNF complex, RSC. Our findings indicate that the histone core of a nucleosome is more plastic than previously imagined and that octamer deformation plays different roles based on the type of chromatin remodeler. Octamer plasticity may contribute to chromatin regulation beyond ATP-dependent remodeling.
三磷酸腺苷（ATP）依赖的染色质重塑酶通过移动核小体DNA发挥重要的生物学作用。然而，尽管受到组蛋白八聚体空间位阻的限制，DNA是如何被移动的仍然未知。通过对一个450千道尔顿的复合物进行甲基横向弛豫优化核磁共振光谱分析，我们发现染色质重塑因子SNF2h会扭曲组蛋白八聚体。处于激活的ATP状态时，SNF2h的结合会改变埋藏的组蛋白残基的动力学。通过位点特异性二硫键连接阻止八聚体扭曲会抑制SNF2h介导的核小体滑动，同时促进SWI-SNF复合物RSC介导的八聚体驱逐。我们的研究结果表明，核小体的组蛋白核心比之前想象的更具可塑性，并且八聚体变形根据染色质重塑因子的类型发挥不同作用。八聚体可塑性可能有助于除ATP依赖的重塑之外的染色质调控。
Zotero 插件