Promoter CpG methylation contributes to ES cell gene regulation in parallel with Oct4/Nanog, PcG complex, and histone H3K4/K27 trimethylation
Promoter CpG methylation contributes to ES cell gene regulation in parallel with Oct4/Nanog, PcG complex, and histone H3K4/K27 trimethylation
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DOI：
10.1016/j.stem.2007.12.011
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发表时间：
2008-02-01
期刊：
影响因子：
23.9
通讯作者：
Fan, Guoping
中科院分区：
文献类型：
--
作者：
Fouse, Shaun D.;Shen, Yin;Fan, Guoping
我们在这里报告了小鼠胚胎干细胞（mES）近端启动子区DNA甲基化模式的全基因组定位。大多数甲基化基因在mES细胞中与分化相关并受到抑制。相比之下，未甲基化的基因组包括许多管家基因和多能性基因。通过将甲基化模式与组蛋白H3赖氨酸（K）4/27三甲基化的全基因组定位以及Oct 4，Nanog和Polycomb蛋白在基因启动子上的结合进行交叉参考，我们发现启动子DNA甲基化是该组中存在于类似30%基因上的唯一标记，其中许多基因在mES细胞中沉默。在去甲基化突变mES细胞中，我们看到X连锁基因和发育基因的一个子集上调，这些基因在野生型mES细胞中甲基化，但缺乏H3 K4和H3 K27三甲基化或与Polycomb，Oct 4或Nanog相关。我们的数据表明，在mES细胞启动子甲基化代表了一个独特的表观遗传程序，补充其他监管机制，以确保适当的基因表达。
We report here genome-wide mapping of DNA methylation patterns at proximal promoter regions in mouse embryonic stem (mES) cells. Most methylated genes are differentiation associated and repressed in mES cells. By contrast, the unmethylated gene set includes many housekeeping and pluripotency genes. By crossreferencing methylation patterns to genome-wide mapping of histone H3 lysine (K) 4/27 trimethylation and binding of Oct4, Nanog, and Polycomb proteins on gene promoters, we found that promoter DNA methylation is the only marker of this group present on similar to 30% of genes, many of which are silenced in mES cells. In demethylated mutant mES cells, we saw upregulation of a subset of X-linked genes and developmental genes that are methylated in wild-type mES cells, but lack either H3K4 and H3K27 trimethylation or association with Polycomb, Oct4, or Nanog. Our data suggest that in mES cells promoter methylation represents a unique epigenetic program that complements other regulatory mechanisms to ensure appropriate gene expression.