SAM Domain Polymerization Links Subnuclear Clustering of PRC1 to Gene Silencing
SAM Domain Polymerization Links Subnuclear Clustering of PRC1 to Gene Silencing
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DOI：
10.1016/j.devcel.2013.08.016
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发表时间：
2013-09-30
影响因子：
11.8
通讯作者：
Koseki, Haruhiko
中科院分区：
文献类型：
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作者：
Isono, Kyoichi;Endo, Takaho A.;Koseki, Haruhiko
Polycomb组（PcG）抑制复合物-1（PRC 1）在细胞核中形成显微镜可见的簇;然而，这种簇形成对转录调控的影响以及调控这一过程的潜在机制仍然不清楚。在这里，我们报告说，PRC 1核心组件Phc 2的无菌α基序（SAM）结构域PRC 1集群通过头到尾的大分子聚合，这是与稳定的目标结合PRC 1/PRC 2和强大的基因沉默活性起着至关重要的作用。我们提出了SAM结构域聚合在这种抑制中的作用，通过两种不同的机制：第一，通过捕获和/或保留PRC 1的PcG目标，第二，通过加强PRC 1和PRC 2之间的相互作用，以稳定转录抑制。我们的研究结果揭示了一种由SAM结构域聚合介导的PcG介导的发育位点抑制的调控机制，该机制使发育过程中的基因抑制程序变得强大而可逆。
The Polycomb-group (PcG) repressive complex-1 (PRC1) forms microscopically visible clusters in nuclei; however, the impact of this cluster formation on transcriptional regulation and the underlying mechanisms that regulate this process remain obscure. Here, we report that the sterile alpha motif (SAM) domain of a PRC1 core component Phc2 plays an essential role for PRC1 clustering through head-to-tail macromolecular polymerization, which is associated with stable target binding of PRC1/PRC2 and robust gene silencing activity. We propose a role for SAM domain polymerization in this repression by two distinct mechanisms: first, through capturing and/or retaining PRC1 at the PcG targets, and second, by strengthening the interactions between PRC1 and PRC2 to stabilize transcriptional repression. Our findings reveal a regulatory mechanism mediated by SAM domain polymerization for PcG-mediated repression of developmental loci that enables a robust yet reversible gene repression program during development.