Graduate Institute of Cancer Biology, China Medical University Taichung 40447, Taiwan ; Center for Molecular Medicine, China Medical University Hospital Taichung 40447, Taiwan.
Am J Transl Res. 2012;4(4):364-75. Epub 2012 Oct 10.
Epigenetic regulation plays an important role in stem cell self-renewal, maintenance and lineage differentiation. The epigenetic profiles of stem cells are related to their transcriptional signature. Enhancer of Zeste homlog 2 (EZH2), a catalytic subunit of epigenetic regulator Polycomb repressive complex 2 (PRC2), has been shown to be a key regulator in controlling cellular differentiation. EZH2 is a histone methyltransferase that not only methylates histone H3 on Lys 27 (H3K27me3) but also interacts with and recruits DNA methyltransferases to methylate CpG at certain EZH2 target genes to establish firm repressive chromatin structures, contributing to tumor progression and the regulation of development and lineage commitment both in embryonic stem cells (ESCs) and adult stem cells. In addition to its well-recognized epigenetic gene silencing function, EZH2 also directly methylates nonhistone targets such as the cardiac transcription factor, GATA4, resulting in attenuated GATA4 transcriptional activity and gene repression. This review addresses recent progress toward the understanding of the biological functions and regulatory mechanisms of EZH2 and its targets as well as their roles in stem cell maintenance and cell differentiation.
表观遗传调控在干细胞自我更新、维持和谱系分化中发挥着重要作用。干细胞的表观遗传特征与其转录特征有关。EZH2（多梳抑制复合物 2 的催化亚基）是一种组蛋白甲基转移酶，不仅可以在赖氨酸 27 上甲基化组蛋白 H3（H3K27me3），还可以与 DNA 甲基转移酶相互作用并募集它们，以甲基化特定 EZH2 靶基因上的 CpG，从而建立牢固的抑制性染色质结构，促进肿瘤的发生发展，并调节胚胎干细胞（ESCs）和成人干细胞中的发育和谱系分化。除了其公认的表观遗传基因沉默功能外，EZH2 还可以直接甲基化非组蛋白靶标，如心脏转录因子 GATA4，导致 GATA4 转录活性和基因抑制减弱。本文综述了 EZH2 及其靶标在干细胞维持和细胞分化中的生物学功能和调控机制及其作用的最新研究进展。
