A core chromatin remodeling factor instructs global chromatin signaling through multivalent reading of nucleosome codes.
A core chromatin remodeling factor instructs global chromatin signaling through multivalent reading of nucleosome codes.
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DOI：
10.1016/j.molcel.2012.12.016
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发表时间：
2013-02-21
期刊：
影响因子：
16
通讯作者：
Kumar, Rakesh
中科院分区：
文献类型：
--
作者：
Nair, Sujit S.;Li, Da-Qiang;Kumar, Rakesh
依赖于ATP的NuRD阻遏复合体涉及其亚基的组合组装。然而，MTA1/NuRD基因转录的机制仍然是个谜。在这里，我们报告了G9a甲基转移酶对MTA1的甲基化和LSD1的去甲基化决定了核小体的重塑和转录结果。与目前NuRD复合体的静态抑制模型相反，我们发现MTA1与核小体和共抑制/共激活复合体是动态的。虽然NuRD阻遏物复合体需要甲基化的MTA1，但去甲基化的MTA1识别二价组蛋白H3K4-AcK9标记，并以信号依赖的方式招募共激活因子NURF-三胸重塑复合体。MTA1‘S赖氨酸532甲基化代表了一种分子开关，即甲基化和去甲基化的MTA1以相反的功能以循环的方式形成具有相反功能的核或NURF复合体。此外，MTA1具有固有的组蛋白放大活性，在影响表观遗传格局方面具有指导作用，为主辅助调节因子的双重辅助调节功能的分子调控提供了新的视角。
ATP-dependent NuRD repressor complexes involve combinatorial assembly of its subunits. However, the mechanism of gene transcription by MTA1/NuRD remains enigmatic. Here we report that MTA1 methylation by G9a methytransferase and demethylation by LSD1 determines the nucleosome remodeling and transcriptional outcome. Contrary to the current static repressor model of the NuRD complex, we discovered that MTA1 association with nucleosomes and co-repressor/ co-activator complexes is dynamic. While methylated MTA1 is required for the NuRD repressor complex, demethylated MTA1 recognizes the bivalent histone H3K4-AcK9 mark and recruits co-activator NURF-trithorax remodeling complex in a signaling-dependent manner. MTA1’s lysine 532 methylation represents a molecular switch as methylated and de-methylated MTA1 nucleate NuRD or NURF complexes with opposite functions in a cyclical manner. In addition, MTA1 possesses an inherent histone amplifier activity with an instructive role in impacting the epigenetic landscape, providing a new perspective to the molecular governance of dual co-regulator functions of a master coregulator.
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