Repression of Somatic Genes by Selective Recruitment of HDAC3 by BLIMP1 Is Essential for Mouse Primordial Germ Cell Fate Determination
Kentaro Mochizuki,
Yohei Hayashi,
Tamotsu Sekinaka,
Kei Otsuka,
Yumi Ito-Matsuoka,
Hisato Kobayashi,
Shinya Oki,
Asuka Takehara,
Tomohiro Kono,
Noriko Osumi,
Yasuhisa Matsui
Affiliations
Kentaro Mochizuki
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
Yohei Hayashi
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
Tamotsu Sekinaka
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
Kei Otsuka
Cell Resource Center for Biomedical Research, Institute of Development, Aging and Cancer (IDAC), Tohoku University, Sendai, Miyagi 980-8575, Japan
Yumi Ito-Matsuoka
Cell Resource Center for Biomedical Research, Institute of Development, Aging and Cancer (IDAC), Tohoku University, Sendai, Miyagi 980-8575, Japan
Hisato Kobayashi
NODAI Genome Research Center, Tokyo University of Agriculture, Tokyo 156-8502, Japan
Shinya Oki
Graduate School of Medical Sciences, Kyushu University, Fukuoka 812-8582, Japan
Asuka Takehara
Cell Resource Center for Biomedical Research, Institute of Development, Aging and Cancer (IDAC), Tohoku University, Sendai, Miyagi 980-8575, Japan
Tomohiro Kono
Department of BioScience, Tokyo University of Agriculture, Tokyo 156-8502, Japan
Noriko Osumi
Department of Developmental Neuroscience, Tohoku University Graduate School of Medicine, Sendai, Miyagi 980-8575, Japan
Yasuhisa Matsui
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; Corresponding author
Summary: 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. : Mochizuki et al. find that targeted histone deacetylation of somatic genes by HDAC3-BLIMP1 represses gene expression, which ensures primordial germ cell fate determination.
