Jarid2 and PRC2, Partner in Regulating Gene Expression

The Polycomb Group proteins foster gene repression profiles required for proper development and unimpaired adulthood, and comprise the components of the PRC2 complex including the histone H3 lysine 27 (H3K27) methyltransferase Ezh2. How mammalian PRC2 accesses chromatin is unclear. We find 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 co-recruitment of PRC2 with resultant increased levels of H3K27me2/3. Jarid2 co-localizes with Ezh2 and MTF2, a homologue of Drosophila Pcl, at endogenous genes in ES cells. Jarid2 can itself 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. Examination of two factors in ES cells

多梳蛋白家族（Polycomb Group proteins）可构建维持正常发育与健康成年所需的基因抑制谱，其作为PRC2复合物的核心组分，包含组蛋白H3赖氨酸27（H3K27）甲基转移酶Ezh2。目前学界对哺乳动物PRC2结合染色质的具体机制尚不明确。本研究发现，Jarid2可与PRC2结合并在体外激活其酶促活性。Jarid2虽含有Jumonji C结构域，但未检测到组蛋白去甲基化酶活性。反之，若在体内将Jarid2人工招募至某启动子区域，可同时招募PRC2，进而提升H3K27me2/3的修饰水平。在胚胎干细胞（embryonic stem cells, ES细胞）中，Jarid2可与Ezh2以及果蝇Pcl（Drosophila Pcl）的同源蛋白MTF2在内源基因位点共定位。Jarid2自身可结合DNA，且其在ES细胞中的招募与PRC2的招募存在相互依存关系：敲低Jarid2会减少其靶启动子区域的PRC2富集，而缺失PRC2组分EED的ES细胞则无法有效招募Jarid2至启动子区域。除已有研究证实的Jarid2下调会导致胚胎存活缺陷外，ES细胞的分化过程及Oct4的沉默均会受到损伤。针对ES细胞中两种因子的相关研究。