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Cell Rep. 2018 Sep 4;24(10):2682-2693.e6. doi: 10.1016/j.celrep.2018.07.108.

Repression of Somatic Genes by Selective Recruitment of HDAC3 by BLIMP1 Is Essential for Mouse Primordial Germ Cell Fate Determination.

Author information

1
Cell Resource Center for Biomedical Research, Institute of Development, Aging and Cancer (IDAC), Tohoku University, Sendai, Miyagi 980-8575, Japan; Center for Environmental Conservation and Research Safety, Tohoku University, Sendai, Miyagi 980-8577, Japan; Graduate School of Life Sciences, Tohoku University, Sendai, Miyagi 980-8577, Japan; Department of Developmental Neuroscience, Tohoku University Graduate School of Medicine, Sendai, Miyagi 980-8575, Japan.
2
Cell Resource Center for Biomedical Research, Institute of Development, Aging and Cancer (IDAC), Tohoku University, Sendai, Miyagi 980-8575, Japan; Graduate School of Life Sciences, Tohoku University, Sendai, Miyagi 980-8577, Japan.
3
Cell Resource Center for Biomedical Research, Institute of Development, Aging and Cancer (IDAC), Tohoku University, Sendai, Miyagi 980-8575, Japan.
4
NODAI Genome Research Center, Tokyo University of Agriculture, Tokyo 156-8502, Japan.
5
Graduate School of Medical Sciences, Kyushu University, Fukuoka 812-8582, Japan.
6
Department of BioScience, Tokyo University of Agriculture, Tokyo 156-8502, Japan.
7
Department of Developmental Neuroscience, Tohoku University Graduate School of Medicine, Sendai, Miyagi 980-8575, Japan.
8
Cell Resource Center for Biomedical Research, Institute of Development, Aging and Cancer (IDAC), Tohoku University, Sendai, Miyagi 980-8575, Japan; Graduate School of Life Sciences, Tohoku University, Sendai, Miyagi 980-8577, Japan; Center for Regulatory Epigenome and Diseases, Tohoku University School of Medicine, Sendai, Miyagi 980-8575, Japan. Electronic address: yasuhisa.matsui.d3@tohoku.ac.jp.

Abstract

Primordial germ cells (PGCs) are fate determined from pluripotent epiblasts. Signaling pathways and transcriptional regulators involved in PGC formation have been identified, but detailed molecular mechanisms of PGC fate determination remains poorly understood. Using RNAi screening, we identified histone deacetylase 3 (HDAC3) as a regulator of PGC formation. Hdac3 deficiency resulted in decreased nascent PGCs in vitro and in vivo, and somatic developmental genes were de-repressed by Hdac3 knockdown during PGC induction. We also demonstrated BLIMP1-dependent enrichment of HDAC3 and deacetylation of H3 and H4 histones in the somatic developmental genes in epiblast-like cells. In addition, the HDAC3/BLIMP1-targeted somatic gene products were enriched in PGC determinant genes; overexpression of these gene products in PGC-like cells in culture resulted in repression of PGC determinant genes. We propose that selective recruitment of HDAC3 to somatic genes by BLIMP1 and subsequent repression of these somatic genes are crucial for PGC fate determination.

PMID:
30184502
DOI:
10.1016/j.celrep.2018.07.108
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