生物
染色质
外胚层
表观遗传学
DNA甲基化
胚胎干细胞
细胞生物学
滋养层
干细胞
遗传学
5-羟甲基胞嘧啶
基因
基因表达
怀孕
胎盘
胎儿
原肠化
作者
Claire E. Senner,Stephanie Chrysanthou,Sarah Burge,Haiyan Lin,Miguel R. Branco,Myriam Hemberger
标识
DOI:10.1016/j.stemcr.2020.04.009
摘要
The ten-eleven translocation factor TET1 and its conferred epigenetic modification 5-hydroxymethylcytosine (5hmC) have important roles in maintaining the pluripotent state of embryonic stem cells (ESCs). We previously showed that TET1 is also essential to maintain the stem cell state of trophoblast stem cells (TSCs). Here, we establish an integrated panel of absolute 5hmC levels, genome-wide DNA methylation and hydroxymethylation patterns, transcriptomes, and TET1 chromatin occupancy in TSCs and differentiated trophoblast cells. We show that the combined presence of 5-methylcytosine (5mC) and 5hmC correlates with transcriptional activity of associated genes. Hypoxia can slow down the global loss of 5hmC that occurs upon differentiation of TSCs. Notably, unlike in ESCs and epiblast cells, most TET1-bound regions overlap with active chromatin marks and TFAP2C binding sites and demarcate putative trophoblast enhancer regions. These chromatin modification and occupancy patterns are highly informative to identify novel candidate regulators of the TSC state.
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