The Arp8 and Arp4 module acts as a DNA sensor controlling INO80 chromatin remodeling.
The Arp8 and Arp4 module acts as a DNA sensor controlling INO80 chromatin remodeling.
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DOI：
10.1038/s41467-018-05710-7
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发表时间：
2018-08-17
影响因子：
16.6
通讯作者：
Bartholomew B
中科院分区：
文献类型：
--
作者：
Brahma S;Ngubo M;Paul S;Udugama M;Bartholomew B
核肌动蛋白和肌动蛋白相关蛋白（Arps）是染色质重塑和修饰复合物的关键组成部分。虽然Arps对于染色质重塑的功能是必不可少的，但其具体作用和机制尚不清楚。在这里，我们定义的核小体结合界面和功能的进化保守的Arps在酵母INO 80染色质重塑复合物。我们发现Arp 8的N-末端、Arp 4的C-末端和Ino 80的HSA结构域与核小体边缘37-51个碱基对的DNA结合，并作为DNA长度传感器调节INO 80的核小体滑动。Arp 8和Arp 4与DNA结合的破坏通过将Arp 5从组蛋白H2 A-H2 B上的酸性补丁和Ino 80-ATP酶结构域从核小体的超螺旋位置（SHL）-6分离来将ATP水解与核小体动员解偶联。我们的数据表明INO 80的Arp 8-Arp 4-actin和Arp 5模块在检测DNA长度、分离核小体和调节核小体定位方面存在功能性相互作用。INO 80染色质重塑蛋白在转录、DNA修复、重组和异染色质维持中起重要作用。在这里，作者阐明了INO 80中肌动蛋白相关蛋白（Arps）之间的功能相互作用，表明Arp 8和Arp 4模块感测分离核小体的DNA长度并调节核小体重塑。
Nuclear actin and actin-related proteins (Arps) are key components of chromatin remodeling and modifying complexes. Although Arps are essential for the functions of chromatin remodelers, their specific roles and mechanisms are unclear. Here we define the nucleosome binding interfaces and functions of the evolutionarily conserved Arps in the yeast INO80 chromatin remodeling complex. We show that the N-terminus of Arp8, C-terminus of Arp4 and the HSA domain of Ino80 bind extranucleosomal DNA 37–51 base pairs from the edge of nucleosomes and function as a DNA-length sensor that regulates nucleosome sliding by INO80. Disruption of Arp8 and Arp4 binding to DNA uncouples ATP hydrolysis from nucleosome mobilization by disengaging Arp5 from the acidic patch on histone H2A-H2B and the Ino80-ATPase domain from the Super-helical Location (SHL) -6 of nucleosomes. Our data suggest a functional interplay between INO80’s Arp8-Arp4-actin and Arp5 modules in sensing the DNA length separating nucleosomes and regulating nucleosome positioning. INO80 chromatin remodeler plays important roles in transcription, DNA repair, recombination, and heterochromatin maintenance. Here the authors characterise the functional interplay between the actin-related proteins (Arps) in INO80, showing that Arp8 and Arp4 module sense the DNA length separating nucleosomes and regulate nucleosome remodeling.
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ISWI染色质重塑器感知核小体修饰以确定底物偏好。
影响因子：
64.8
作者：
Dann GP;Liszczak GP;Bagert JD;Müller MM;Nguyen UTT;Wojcik F;Brown ZZ;Bos J;Panchenko T;Pihl R;Pollock SB;Diehl KL;Allis CD;Muir TW
通讯作者：
Muir TW
影响因子：
16.6
作者：
Watanabe, Shinya;Tan, Dongyan;Lakshminarasimhan, Mahadevan;Washburn, Michael P.;Hong, Eun-Jin Erica;Walz, Thomas;Peterson, Craig L.
通讯作者：
Peterson, Craig L.
影响因子：
64.8
作者：
Ayala R;Willhoft O;Aramayo RJ;Wilkinson M;McCormack EA;Ocloo L;Wigley DB;Zhang X
通讯作者：
Zhang X
影响因子：
9.8
作者：
Guo, Dong-chuan;Duan, Xue-Yan;Milewicz, Dianna M.
通讯作者：
Milewicz, Dianna M.
影响因子：
64.5
作者：
Morrison, AJ;Highland, J;Shen, XT
通讯作者：
Shen, XT