Composition and histone substrates of polycomb repressive group complexes change during cellular differentiation
Composition and histone substrates of polycomb repressive group complexes change during cellular differentiation
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DOI：
10.1073/pnas.0409875102
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发表时间：
2005-02-08
影响因子：
11.1
通讯作者：
Reinberg, D
中科院分区：
文献类型：
--
作者：
Kuzmichev, A;Margueron, R;Reinberg, D
不可逆地改变染色质组蛋白成分的因子的底物特异性的变化，预计将通过表观遗传学对基因表达产生深远的影响。EZH2是一种组蛋白-赖氨酸甲基转移酶，其活性取决于它与多梳抑制复合体2和3(PRC2/3)的其他成分的结合。在前列腺癌进展过程中，EZH2水平越来越高。其他PRC2/3组分在癌细胞中也升高。Ezh2在组织培养中的过表达促进了以前未描述的PRC复合体PrC4的形成，该复合体包含依赖NAD(+)的组蛋白去乙酰基酶SirT1和PRC组分Eed的异构体2。Eed2在癌症和未分化的胚胎干细胞中表达，但在正常和分化的ES细胞中检测不到。不同的PRC-S表现出不同的组蛋白底物特异性。这些发现表明，转化特异性PRC复合体的形成可能通过调节染色质结构在重置基因表达模式方面发挥重要作用。
Changes in the substrate specificities of factors that irreversibly modify the histone components of chromatin are expected to have a profound effect on gene expression through epigenetics. Ezh2 is a histone-lysine methyltransferase with activity dependent on its association with other components of the Polycomb Repressive Complexes 2 and 3 (PRC2/3). Ezh2 levels are increasingly elevated during prostate cancer progression. Other PRC2/3 components also are elevated in cancer cells. Overexpression of Ezh2 in tissue culture promotes formation of a previously undescribed PRC complex, PRC4, that contains the NAD(+)-dependent histone deacetylase SirT1 and isoform 2 of the PRC component Eed. Eed2 is expressed in cancer and undifferentiated embryonic stem (ES) cells but is undetectable in normal and differentiated ES cells. The distinct PRC-s exhibit differential histone substrate specificities. These findings suggest that formation of a transformation-specific PRC complex may have a major role in resetting patterns of gene expression by regulating chromatin structure.