Cdt1-binding protein GRWD1 is a novel histone-binding protein that facilitates MCM loading through its influence on chromatin architecture.
Cdt1-binding protein GRWD1 is a novel histone-binding protein that facilitates MCM loading through its influence on chromatin architecture.
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DOI：
10.1093/nar/gkv509
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发表时间：
2015-07-13
影响因子：
14.9
通讯作者：
Fujita M
中科院分区：
文献类型：
--
作者：
Sugimoto N;Maehara K;Yoshida K;Yasukouchi S;Osano S;Watanabe S;Aizawa M;Yugawa T;Kiyono T;Kurumizaka H;Ohkawa Y;Fujita M
在染色质模板上有效地形成复制前复合物（pre-RC）对于维持基因组完整性至关重要。然而，在这一过程中的染色质动力学的调节仍然是难以捉摸的。我们发现，一个保守的蛋白质，GRWD 1（谷氨酸丰富的WD 40重复包含1），结合到两个代表性的复制起点，特别是在G1期的CDC 6和Cdt 1依赖的方式，和GRWD 1的耗尽减少负载的MCM，但不是CDC 6和Cdt 1。此外，染色质免疫沉淀结合高通量测序（Seq）揭示了GRWD 1与CDC 6的显著全基因组共定位。我们发现GRWD 1具有组蛋白结合活性。为了研究GRWD 1对染色质结构的影响，我们使用了甲醛辅助分离调控元件（FAIRE）-seq或FAIRE-定量PCR分析，结果表明GRWD 1在特定的染色质位置调节染色质开放。两者合计，这些研究结果表明，GRWD 1可能是一种新的组蛋白结合蛋白，调节染色质动力学和MCM加载在复制起点。
Efficient pre-replication complex (pre-RC) formation on chromatin templates is crucial for the maintenance of genome integrity. However, the regulation of chromatin dynamics during this process has remained elusive. We found that a conserved protein, GRWD1 (glutamate-rich WD40 repeat containing 1), binds to two representative replication origins specifically during G1 phase in a CDC6- and Cdt1-dependent manner, and that depletion of GRWD1 reduces loading of MCM but not CDC6 and Cdt1. Furthermore, chromatin immunoprecipitation coupled with high-throughput sequencing (Seq) revealed significant genome-wide co-localization of GRWD1 with CDC6. We found that GRWD1 has histone-binding activity. To investigate the effect of GRWD1 on chromatin architecture, we used formaldehyde-assisted isolation of regulatory elements (FAIRE)-seq or FAIRE-quantitative PCR analyses, and the results suggest that GRWD1 regulates chromatin openness at specific chromatin locations. Taken together, these findings suggest that GRWD1 may be a novel histone-binding protein that regulates chromatin dynamics and MCM loading at replication origins.
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DOI：
10.1083/jcb.201109105
发表时间：
2012-08-20
期刊：
The Journal of cell biology
影响因子：
--
作者：
Papior P;Arteaga-Salas JM;Günther T;Grundhoff A;Schepers A
通讯作者：
Schepers A
影响因子：
64.8
作者：
Dominguez-Sola, David;Ying, Carol Y.;Dalla-Favera, Riccardo
通讯作者：
Dalla-Favera, Riccardo
影响因子：
7
作者：
Cayrou, Christelle;Coulombe, Philippe;Mechali, Marcel
通讯作者：
Mechali, Marcel
影响因子：
16.8
作者：
Besnard, Emilie;Babied, Amelie;Lemaitre, Jean-Marc
通讯作者：
Lemaitre, Jean-Marc
影响因子：
7
作者：
MacAlpine, Heather K.;Gordan, Raluca;MacAlpine, David M.
通讯作者：
MacAlpine, David M.