Howard Hughes Medical Institute, Department of Biochemistry and Molecular Pharmacology, New York University School of Medicine, New York, New York 10016, USA;
Genes Dev. 2013 Dec 15;27(24):2663-77. doi: 10.1101/gad.225888.113.
Polycomb-repressive complex 2 (PRC2) comprises specific members of the Polycomb group of epigenetic modulators. PRC2 catalyzes methylation of histone H3 at Lys 27 (H3K27me3) through its Enhancer of zeste (Ezh) constituent, of which there are two mammalian homologs: Ezh1 and Ezh2. Several ancillary factors, including Jarid2, modulate PRC2 function, with Jarid2 facilitating its recruitment to target genes. Jarid2, like Ezh2, is present in poorly differentiated and actively dividing cells, while Ezh1 associates with PRC2 in all cells, including resting cells. We found that Jarid2 exhibits nucleosome-binding activity that contributes to PRC2 stimulation. Moreover, such nucleosome-binding activity is exhibited by PRC2 comprising Ezh1 (PRC2-Ezh1), in contrast to PRC2-Ezh2. The presence of Ezh1 helps to maintain PRC2 occupancy on its target genes in myoblasts where Jarid2 is not expressed. Our findings allow us to propose a model in which PRC2-Ezh2 is important for the de novo establishment of H3K27me3 in dividing cells, whereas PRC2-Ezh1 is required for its maintenance in resting cells.
多梳抑制复合物 2（PRC2）包含特定的表观遗传调节剂多梳组蛋白成员。PRC2 通过其组成部分 Enhancer of zeste（Ezh）催化组蛋白 H3 赖氨酸 27（H3K27me3）的甲基化，其中有两个哺乳动物同源物：Ezh1 和 Ezh2。几种辅助因子，包括 Jarid2，调节 PRC2 的功能，Jarid2 促进其募集到靶基因。Jarid2 像 Ezh2 一样，存在于分化不良和活跃分裂的细胞中，而 Ezh1 与所有细胞中的 PRC2 相关联，包括静止细胞。我们发现 Jarid2 表现出核小体结合活性，有助于 PRC2 的刺激。此外，包含 Ezh1 的 PRC2（PRC2-Ezh1）表现出这种核小体结合活性，而 PRC2-Ezh2 则没有。Ezh1 的存在有助于在不表达 Jarid2 的成肌细胞中维持 PRC2 对其靶基因的占据。我们的发现使我们能够提出一个模型，即 PRC2-Ezh2 对于分裂细胞中 H3K27me3 的从头建立很重要，而 PRC2-Ezh1 对于其在静止细胞中的维持是必需的。
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