Bmi1 cooperates with Dnmt1-associated protein 1 in gene silencing
Bmi1 cooperates with Dnmt1-associated protein 1 in gene silencing
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DOI：
10.1016/j.bbrc.2006.12.166
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发表时间：
2007-02-23
影响因子：
3.1
通讯作者：
Iwama, Atsushi
中科院分区：
文献类型：
--
作者：
Negishi, Masamitsu;Saraya, Atsunori;Iwama, Atsushi
Polycomb group （PcG）蛋白通过染色质修饰参与基因沉默。在多梳抑制复合物（PRCs）中，PRC1表现出H2A-KI 19泛素E3连接酶活性。然而，prc1介导的基因沉默的分子机制在很大程度上仍然不清楚。在这项研究中，我们发现Bmi1直接与drant相关蛋白1 （Dmapl）相互作用，Dmapl已被表征为与维持DNA甲基转移酶Dnmt1相关。Bmil与Dmapl和Dnmtl形成三元配合物，Dmapl位于中心位置。染色质免疫沉淀证实了PRC1在Bmil靶位点的三元复合物形成。Dmapl与Bmil靶位点结合的缺失与Bmil（-/-）细胞中基因表达的降低密切相关。Dmap1敲除与Bmil敲除对Bmil靶点（包括Hox基因）表达的影响相同。总的来说，我们的研究结果表明Bmil在多梳基因沉默中包含Dmap1。(c) 2006爱思唯尔公司版权所有。
Polycomb group (PcG) proteins are involved in gene silencing through chromatin modifications. Among polycomb repressive complexes (PRCs), PRC1 exhibits H2A-KI 19 ubiquitin E3 ligase activity. However, the molecular mechanisms underlying PRC1-mediated gene silencing remain largely obscure. In this study, we found that Bmi1 directly interacts with Drant-associated protein 1 (Dmapl), which has been characterized to associate with the maintenance DNA methyltransferase, Dnmt1. Bmil was demonstrated to form a ternary complex with Dmapl and Dnmtl with Dmapl in the central position. Chromatin immunoprecipitations confirmed the ternary complex formation within the context of the PRC1 at the Bmil target loci. Loss of Dmapl binding to the Bmil target loci was tightly associated with derepressed gene expression in Bmil(-/-) cells. Dmap1 knockdown exhibited the same impact as Bmil knockout did on the expression of Bmil targets, including Hox genes. Collectively, our findings suggest that Bmil incorporates Dmap1 in polycomb gene silencing. (c) 2006 Elsevier Inc. All rights reserved.