RRC ID 54147
Author Mochizuki K, Hayashi Y, Sekinaka T, Otsuka K, Ito-Matsuoka Y, Kobayashi H, Oki S, Takehara A, Kono T, Osumi N, Matsui Y.
Title Repression of Somatic Genes by Selective Recruitment of HDAC3 by BLIMP1 Is Essential for Mouse Primordial Germ Cell Fate Determination.
Journal Cell Rep
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.
Volume 24(10)
Pages 2682-2693.e6
Published 2018-9-4
DOI 10.1016/j.celrep.2018.07.108
PII S2211-1247(18)31241-5
PMID 30184502
MeSH Acetylation Animals Gene Expression Regulation, Developmental Germ Cells / metabolism* Histone Deacetylases / genetics Histone Deacetylases / metabolism* Histones / metabolism Mice Positive Regulatory Domain I-Binding Factor 1 / genetics Positive Regulatory Domain I-Binding Factor 1 / metabolism* Signal Transduction / genetics Signal Transduction / physiology Transcription Factors / genetics Transcription Factors / metabolism
IF 8.109
Times Cited 4
DNA material CSII-EF-MCS (RDB04378) pCAG-HIVgp (RDB04394) pCMV-VSV-G-RSV-Rev (RDB04393)
Mice RBRC01830