Jarid2 and PRC2, partners in regulating gene expression
Jarid2 and PRC2, partners in regulating gene expression
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DOI：
10.1101/gad.1886410
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发表时间：
2010-02-15
影响因子：
10.5
通讯作者：
Reinberg, Danny
中科院分区：
文献类型：
--
作者：
Li, Gang;Margueron, Raphael;Reinberg, Danny
Polycomb组蛋白促进正常发育和未受损成年期所需的基因抑制谱，并包含Polycomb抑制复合物2（PRC 2）的组分，包括组蛋白H3 Lys 27（H3 K27）甲基转移酶Ezh 2。哺乳动物PRC 2如何进入染色质尚不清楚。我们发现Jarid 2与PRC 2结合并在体外刺激其酶活性。Jarid 2含有一个Jumonji C结构域，但没有可检测的组蛋白去甲基化酶活性。相反，其在体内人工募集到启动子导致PRC 2的共募集，从而增加H3 K27（H3 K27 me 2/3）的二甲基化和三甲基化水平。Jarid 2与Ezh 2和MTF 2（果蝇Pcl的同源物）共定位于胚胎干（ES）细胞中的内源基因。Jarid 2可以结合DNA，并且其在ES细胞中的募集与PRC 2的募集是相互依赖的，因为Jarid 2敲低在其靶启动子处减少PRC 2，并且缺乏PRC 2组分EED的ES细胞在Jarid 2启动子接近方面是缺陷的。除了在下调Jarid 2时胚胎活力的充分记录的缺陷之外，ES细胞分化受损，Oct 4沉默也是如此。
The Polycomb group proteins foster gene repression profiles required for proper development and unimpaired adulthood, and comprise the components of the Polycomb-Repressive Complex 2 (PRC2) including the histone H3 Lys 27 (H3K27) methyltransferase Ezh2. How mammalian PRC2 accesses chromatin is unclear. We found that Jarid2 associates with PRC2 and stimulates its enzymatic activity in vitro. Jarid2 contains a Jumonji C domain, but is devoid of detectable histone demethylase activity. Instead, its artificial recruitment to a promoter in vivo resulted in corecruitment of PRC2 with resultant increased levels of di- and trimethylation of H3K27 (H3K27me2/3). Jarid2 colocalizes with Ezh2 and MTF2, a homolog of Drosophila Pcl, at endogenous genes in embryonic stem (ES) cells. Jarid2 can bind DNA and its recruitment in ES cells is interdependent with that of PRC2, as Jarid2 knockdown reduced PRC2 at its target promoters, and ES cells devoid of the PRC2 component EED are deficient in Jarid2 promoter access. In addition to the well-documented defects in embryonic viability upon down-regulation of Jarid2, ES cell differentiation is impaired, as is Oct4 silencing.