@article{61dccaae854e4c2488d4bbbbb956b2fb,
title = "Repression of Somatic Genes by Selective Recruitment of HDAC3 by BLIMP1 Is Essential for Mouse Primordial Germ Cell Fate Determination",
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. Mochizuki et al. find that targeted histone deacetylation of somatic genes by HDAC3-BLIMP1 represses gene expression, which ensures primordial germ cell fate determination.",
author = "Kentaro Mochizuki and Yohei Hayashi and Tamotsu Sekinaka and Kei Otsuka and Yumi Ito-Matsuoka and Hisato Kobayashi and Shinya Oki and Asuka Takehara and Tomohiro Kono and Noriko Osumi and Yasuhisa Matsui",
note = "Funding Information: We thank Drs. Mitinori Saitou and Yukihiro Yabuta for Blimp1::Venus/Stella::CFP (BVSC) ESCs and RNA-seq data files, Dr. Katsuhiko Hayashi for technical advice for PGCLC induction, and Dr. Tatsuya Takemoto for technical advice for the Cas9-electroporation system. We also thank Drs. Jafar Sharif, Masaki Hosogane, Eri Hosogane-Kobayashi, Daiji Okamura, Ari Itoh-Nakadai, Akihiko Muto, Satomi Tanaka, and Katsuyoshi Takaoka and all members of Cell Resource Center for Biomedical Research for helpful discussions and the Biomedical Research Core of Tohoku University Graduate School of Medicine and the Center of Research Instruments of Institute of Development, Aging and Cancer (IDAC), Tohoku University, for use of instruments and technical support. K.M. was supported by a Grant-in-Aid for Scientific Researh (KAKENHI) for Young Scientists (B) (grant 17K17594) from the Ministry of Education, Culture, Sports, Science and Technology of Japan (MEXT) and by the Inamori Foundation , the Gonryo Foundation for Promotion of Medical Sciences , and the Kawano Masanori Memorial Public Interest Incorporated Foundation for Promotion of Pediatrics . Y.H. was supported by KAKENHI in the Innovative Areas, “Sex Spectrum” (grant 18H04875 ) from MEXT and by the Uehara Memorial Foundation , a Grant for Basic Science Research Projects from the Sumitomo Foundation , and the Joint Usage and Joint Research Programs, Institute of Advanced Medical Sciences, Tokushima University. H.K. was supported by the MEXT-Supported Program for the Strategic Research Foundation at Private Universities, 2013–2017 ( S1311017 ) from MEXT . N.O. was supported by KAKENHI in the Innovative Areas (grant 16H06530 ) from MEXT. Y.M. was supported by KAKENHI in the Innovative Areas, “Mechanisms Regulating Gamete Formation in Animals” (grant 25114003 ) from MEXT and by AMED-CREST (grant JP17gm0510017h ) from the Japan Agency for Medical Research and Development . Funding Information: We thank Drs. Mitinori Saitou and Yukihiro Yabuta for Blimp1::Venus/Stella::CFP (BVSC) ESCs and RNA-seq data files, Dr. Katsuhiko Hayashi for technical advice for PGCLC induction, and Dr. Tatsuya Takemoto for technical advice for the Cas9-electroporation system. We also thank Drs. Jafar Sharif, Masaki Hosogane, Eri Hosogane-Kobayashi, Daiji Okamura, Ari Itoh-Nakadai, Akihiko Muto, Satomi Tanaka, and Katsuyoshi Takaoka and all members of Cell Resource Center for Biomedical Research for helpful discussions and the Biomedical Research Core of Tohoku University Graduate School of Medicine and the Center of Research Instruments of Institute of Development, Aging and Cancer (IDAC), Tohoku University, for use of instruments and technical support. K.M. was supported by a Grant-in-Aid for Scientific Researh (KAKENHI) for Young Scientists (B) (grant 17K17594) from the Ministry of Education, Culture, Sports, Science and Technology of Japan (MEXT) and by the Inamori Foundation, the Gonryo Foundation for Promotion of Medical Sciences, and the Kawano Masanori Memorial Public Interest Incorporated Foundation for Promotion of Pediatrics. Y.H. was supported by KAKENHI in the Innovative Areas, “Sex Spectrum” (grant 18H04875) from MEXT and by the Uehara Memorial Foundation, a Grant for Basic Science Research Projects from the Sumitomo Foundation, and the Joint Usage and Joint Research Programs, Institute of Advanced Medical Sciences, Tokushima University. H.K. was supported by the MEXT-Supported Program for the Strategic Research Foundation at Private Universities, 2013–2017 (S1311017) from MEXT. N.O. was supported by KAKENHI in the Innovative Areas (grant 16H06530) from MEXT. Y.M. was supported by KAKENHI in the Innovative Areas, “Mechanisms Regulating Gamete Formation in Animals” (grant 25114003) from MEXT and by AMED-CREST (grant JP17gm0510017h) from the Japan Agency for Medical Research and Development. Publisher Copyright: {\textcopyright} 2018 The Author(s)",
year = "2018",
month = sep,
day = "4",
doi = "10.1016/j.celrep.2018.07.108",
language = "English",
volume = "24",
pages = "2682--2693.e6",
journal = "Cell Reports",
issn = "2211-1247",
publisher = "Cell Press",
number = "10",
}