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.

10-11 易位因子 TET1 及其赋予的表观遗传修饰 5-羟甲基胞嘧啶 (5hmC) 在维持胚胎干细胞 (ESC) 的多能状态方面具有重要作用。我们之前表明 TET1 对于维持滋养层干细胞 (TSC) 的干细胞状态也是必不可少的。在这里，我们建立了一个包含绝对 5hmC 水平、全基因组 DNA 甲基化和羟甲基化模式、转录组和 TSC 和分化滋养层细胞中 TET1 染色质占有率的综合面板。我们表明 5-甲基胞嘧啶 (5mC) 和 5hmC 的组合存在与相关基因的转录活性相关。缺氧可以减缓 TSC 分化时发生的 5hmC 的整体损失。值得注意的是，与 ESC 和外胚层细胞不同，大多数 TET1 结合区域与活性染色质标记和 TFAP2C 结合位点重叠，并划分出推定的滋养层增强子区域。这些染色质修饰和占用模式对于识别 TSC 状态的新候选调节剂具有很高的信息量。