Distinct DNA methylation patterns characterize differentiated human embryonic stem cells and developing human fetal liver
Distinct DNA methylation patterns characterize differentiated human embryonic stem cells and developing human fetal liver
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DOI：
10.1101/gr.088773.108
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发表时间：
2009-06-01
期刊：
影响因子：
7
通讯作者：
Myers, Richard M.
中科院分区：
文献类型：
--
作者：
Brunner, Alayne L.;Johnson, David S.;Myers, Richard M.
为了研究DNA甲基化在人类发育过程中的作用，我们开发了Methyl-seq，这是一种在整个基因组中超过90，000个区域检测DNA甲基化的方法。对人类胚胎干细胞（hESC），其衍生物和人类组织进行甲基测序使我们能够确定hESC和体内肝脏分化过程中的几种趋势。首先，分化导致在体外和体内（2%-11%）的最小数量的测定区域的DNA甲基化变化。第二，在体外hESC分化的特点是从头甲基化和去甲基化，而在体内胎肝发育的特点是主要由去甲基化。第三，hESC分化的独特特征是甲基化变化，特别是在H3 K27 me 3占据的区域，二价结构域，和低密度CpG启动子（LCP），这表明这些区域更有可能参与hESC分化过程中的转录调控。尽管H3 K27 me 3占据的结构域和LCP也是人类肝脏发育过程中DNA甲基化状态的高变异性区域，但这些区域变得高度未甲基化，这与在hESC中观察到的趋势不同。综上所述，我们的结果表明，hESC分化具有独特的DNA甲基化特征，这可能不是体内分化的指示。
To investigate the role of DNA methylation during human development, we developed Methyl-seq, a method that assays DNA methylation at more than 90,000 regions throughout the genome. Performing Methyl-seq on human embryonic stem cells (hESCs), their derivatives, and human tissues allowed us to identify several trends during hESC and in vivo liver differentiation. First, differentiation results in DNA methylation changes at a minimal number of assayed regions, both in vitro and in vivo (2%-11%). Second, in vitro hESC differentiation is characterized by both de novo methylation and demethylation, whereas in vivo fetal liver development is characterized predominantly by demethylation. Third, hESC differentiation is uniquely characterized by methylation changes specifically at H3K27me3-occupied regions, bivalent domains, and low density CpG promoters (LCPs), suggesting that these regions are more likely to be involved in transcriptional regulation during hESC differentiation. Although both H3K27me3-occupied domains and LCPs are also regions of high variability in DNA methylation state during human liver development, these regions become highly unmethylated, which is a distinct trend from that observed in hESCs. Taken together, our results indicate that hESC differentiation has a unique DNA methylation signature that may not be indicative of in vivo differentiation.