The TFAP2C-Regulated OCT4 Naive Enhancer Is Involved in Human Germline Formation

被引：60

作者：

Chen, Di ^{[1
]}

Liu, Wanlu ^{[2
]}

Zimmerman, Jill ^{[1
]}

Pastor, William A. ^{[1
,9
]}

Kim, Rachel ^{[3
]}

Hosohama, Linzi ^{[1
]}

Ho, Jamie ^{[1
]}

Aslanyan, Marianna ^{[1
]}

Gell, Joanna J. ^{[4
,5
]}

Jacobsen, Steven E. ^{[1
,2
,3
,6
,7
]}

Clark, Amander T. ^{[1
,2
,3
,8
]}

机构：

[1] Univ Calif Los Angeles, Dept Mol Cell & Dev Biol, Los Angeles, CA 90095 USA

[2] Univ Calif Los Angeles, Inst Mol Biol, Los Angeles, CA 90024 USA

[3] Univ Calif Los Angeles, Eli & Edythe Broad Ctr Regenerat Med & Stem Cell, Los Angeles, CA 90095 USA

[4] Dept Pediat, Div Hematol Oncol, Los Angeles, CA 90095 USA

[5] David Geffen Sch Med, Los Angeles, CA 90095 USA

[6] Univ Calif Los Angeles, Dept Biol Chem, Los Angeles, CA 90024 USA

[7] Univ Calif Los Angeles, Howard Hughes Med Inst, Los Angeles, CA 90024 USA

[8] Univ Calif Los Angeles, Jonsson Comprehens Canc Ctr, Los Angeles, CA 90024 USA

[9] McGill Univ, Dept Biochem, Montreal, PQ H3G 1Y6, Canada

来源：

CELL REPORTS | 2018年 / 25卷 / 13期

关键词：

CELL SPECIFICATION; DNA METHYLATION; PLURIPOTENCY; INDUCTION; FATE; PRINCIPLES; MONKEYS; CULTURE; STATES;

D O I：

10.1016/j.celrep.2018.12.011

中图分类号：

Q2 [细胞生物学];

学科分类号：

071009 ; 090102 ;

摘要：

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.

引用

页码：3591 / +

页数：17

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