The TFAP2C-Regulated OCT4 Naive Enhancer Is Involved in Human Germline Formation
The TFAP2C-Regulated OCT4 Naive Enhancer Is Involved in Human Germline Formation
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DOI：
10.1016/j.celrep.2018.12.011
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发表时间：
2018-12-26
期刊：
影响因子：
8.8
通讯作者：
Clark, Amander T.
中科院分区：
文献类型：
--
作者：
Chen, Di;Liu, Wanlu;Clark, Amander T.
人类原始生殖细胞（hPGC）是生殖细胞谱系中最早的胚胎祖细胞，但其形成所需的分子机制尚未得到很好的表征。为了确定hPGC发育中的调控区域，我们使用转座酶可及染色质测序（ATAC-seq）方法系统地表征了人胚胎干细胞（hESCs）分化的hPGC和hPGC样细胞（hpgclc）中的开放染色质区域。我们发现了hPGCs和hpgclc特有的开放染色质区域，这些区域与在多能性初始基态中鉴定的tfap2c结合增强子显著重叠。使用CRISPR/Cas9，我们发现删除OCT4位点上的tfap2c结合的初始增强子（也称为POU5F1）会导致OCT4表达受损，并对hPGCLC的身份产生负面影响。
Human primordial germ cells (hPGCs) are the first embryonic progenitors in the germ cell lineage, yet the molecular mechanisms required for hPGC formation are not well characterized. To identify regulatory regions in hPGC development, we used the assay for transposase-accessible chromatin using sequencing (ATAC-seq) to systematically characterize regions of open chromatin in hPGCs and hPGC-like cells (hPGCLCs) differentiated from human embryonic stem cells (hESCs). We discovered regions of open chromatin unique to hPGCs and hPGCLCs that significantly overlap with TFAP2C-bound enhancers identified in the naive ground state of pluripotency. Using CRISPR/Cas9, we show that deleting the TFAP2C-bound naive enhancer at the OCT4 locus (also called POU5F1) results in impaired OCT4 expression and a negative effect on hPGCLC identity.