Hernández-Muñoz Inmaculada, Taghavi Panthea, Kuijl Coenraad, Neefjes Jacques, van Lohuizen Maarten
Division of Molecular Genetics, The Netherlands Cancer Institute, Amsterdam.
Mol Cell Biol. 2005 Dec;25(24):11047-58. doi: 10.1128/MCB.25.24.11047-11058.2005.
Polycomb group (PcG) proteins are epigenetic chromatin modifiers involved in heritable gene repression. Two main PcG complexes have been characterized. Polycomb repressive complex 2 (PRC2) is thought to be involved in the initiation of gene silencing, whereas Polycomb repressive complex 1 (PRC1) is implicated in the stable maintenance of gene repression. Here, we investigate the kinetic properties of the binding of one of the PRC1 core components, BMI1, with PcG bodies. PcG bodies are unique nuclear structures located on regions of pericentric heterochromatin, found to be the site of accumulation of PcG complexes in different cell lines. We report the presence of at least two kinetically different pools of BMI1, a highly dynamic and a less dynamic fraction, which may reflect BMI1 pools with different binding capacities to these stable heterochromatin domains. Interestingly, PRC2 members EED and EZH2 appear to be essential for BMI1 recruitment to the PcG bodies. Furthermore, we demonstrate that the maintenance DNA methyltransferase DNMT1 is necessary for proper PcG body assembly independent of DNMT-associated histone deacetylase activity. Together, these results provide new insights in the mechanism for regulation of chromatin silencing by PcG proteins and suggest a highly regulated recruitment of PRC1 to chromatin.
多梳蛋白家族(PcG)是参与遗传性基因抑制的表观遗传染色质修饰因子。已鉴定出两种主要的PcG复合物。多梳抑制复合物2(PRC2)被认为参与基因沉默的起始,而多梳抑制复合物1(PRC1)则与基因抑制的稳定维持有关。在此,我们研究了PRC1核心成分之一BMI1与PcG小体结合的动力学特性。PcG小体是位于着丝粒周围异染色质区域的独特核结构,被发现是不同细胞系中PcG复合物积累的位点。我们报告了至少存在两个动力学不同的BMI1池,一个高度动态的池和一个动态性较低的池,这可能反映了BMI1对这些稳定异染色质结构域具有不同结合能力的池。有趣的是,PRC2成员EED和EZH2似乎对于BMI1募集到PcG小体至关重要。此外,我们证明维持性DNA甲基转移酶DNMT1对于适当的PcG小体组装是必需的,且不依赖于与DNMT相关的组蛋白去乙酰化酶活性。总之,这些结果为PcG蛋白调控染色质沉默的机制提供了新见解,并提示PRC1向染色质的募集受到高度调控。