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

Di Chen; Wanlu Liu; Jill Zimmerman; William A. Pastor; Rachel Kim; Linzi Hosohama; Jamie Ho; Marianna Aslanyan; Joanna J. Gell; Steven E. Jacobsen; Amander T. Clark

Cell Reports (Dec 2018)

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

Di Chen,
Wanlu Liu,
Jill Zimmerman,
William A. Pastor,
Rachel Kim,
Linzi Hosohama,
Jamie Ho,
Marianna Aslanyan,
Joanna J. Gell,
Steven E. Jacobsen,
Amander T. Clark

Affiliations

Di Chen: Department of Molecular Cell and Developmental Biology, University of California, Los Angeles, Los Angeles, CA, USA
Wanlu Liu: Molecular Biology Institute, University of California, Los Angeles, Los Angeles, CA, USA
Jill Zimmerman: Department of Molecular Cell and Developmental Biology, University of California, Los Angeles, Los Angeles, CA, USA
William A. Pastor: Department of Molecular Cell and Developmental Biology, University of California, Los Angeles, Los Angeles, CA, USA
Rachel Kim: Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research, University of California, Los Angeles, Los Angeles, CA, USA
Linzi Hosohama: Department of Molecular Cell and Developmental Biology, University of California, Los Angeles, Los Angeles, CA, USA
Jamie Ho: Department of Molecular Cell and Developmental Biology, University of California, Los Angeles, Los Angeles, CA, USA
Marianna Aslanyan: Department of Molecular Cell and Developmental Biology, University of California, Los Angeles, Los Angeles, CA, USA
Joanna J. Gell: Department of Pediatrics, Division of Hematology-Oncology, Los Angeles, CA 90095, USA; David Geffen School of Medicine, Los Angeles, CA 90095, USA
Steven E. Jacobsen: Department of Molecular Cell and Developmental Biology, University of California, Los Angeles, Los Angeles, CA, USA; Molecular Biology Institute, University of California, Los Angeles, Los Angeles, CA, USA; Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research, University of California, Los Angeles, Los Angeles, CA, USA; Department of Biological Chemistry, University of California, Los Angeles, Los Angeles, CA, USA; Howard Hughes Medical Institute, University of California, Los Angeles, Los Angeles, CA, USA
Amander T. Clark: Department of Molecular Cell and Developmental Biology, University of California, Los Angeles, Los Angeles, CA, USA; Molecular Biology Institute, University of California, Los Angeles, Los Angeles, CA, USA; Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research, University of California, Los Angeles, Los Angeles, CA, USA; Jonsson Comprehensive Cancer Center, University of California, Los Angeles, Los Angeles, CA, USA; Corresponding author

Journal volume & issue: Vol. 25, no. 13
pp. 3591 – 3602.e5

Abstract

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Summary: 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. : Combining genomics and functional studies, Chen et al. identify the open chromatin state of human primordial germ cells (hPGCs), leading to the discovery that TFAP2C regulates hPGC development through the opening of naive enhancers. Keywords: TFAP2C, OCT4, naive, enhancer, PGC, PGCLC, pluripotency

Published in Cell Reports

ISSN: 2211-1247 (Online)
Publisher: Elsevier
Country of publisher: Netherlands
LCC subjects: Science: Biology (General)
Website: http://www.cell.com/cell-reports/home

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