title: PRDM14 Drives OCT3/4 Recruitment via Active Demethylation in the Transition from Primed to Naive Pluripotency.
abstract: Primordial germ cells (PGCs) are specified from epiblast cells in mice. Genes associated with naive pluripotency are repressed in the transition from inner cell mass to epiblast cells, followed by upregulation after PGC specification. However, the molecular mechanisms underlying the reactivation of pluripotency genes are poorly characterized. Here, we exploited the in vitro differentiation of epiblast-like cells (EpiLCs) from embryonic stem cells (ESCs) to elucidate the molecular and epigenetic functions of PR domain-containing 14 (PRDM14). We found that Prdm14 overexpression in EpiLCs induced their conversion to ESC-like cells even in the absence of leukemia inhibitory factor in adherent culture. This was impaired by the loss of Kruppel-like factor 2 and ten-eleven translocation (TET) proteins. Furthermore, PRDM14 recruited OCT3/4 to the enhancer regions of naive pluripotency genes via TET-base excision repair-mediated demethylation. Our results provide evidence that PRDM14 establishes a transcriptional network for naive pluripotency via active DNA demethylation.
authors.affiliation: Department of Biomedical Chemistry, School of Science and Technology, Kwansei Gakuin University, 2-1, Gakuen, Sanda, Hyogo 669-1337, Japan; Department of Enzyme Chemistry, Institute for Enzyme Research, Tokushima University, Tokushima 770-8503, Japan.
authors.forename: Naoki
authors.initials: N
authors.lastname: Okashita
authors.affiliation: Department of Biomedical Chemistry, School of Science and Technology, Kwansei Gakuin University, 2-1, Gakuen, Sanda, Hyogo 669-1337, Japan.
authors.forename: Yoshiaki
authors.initials: Y
authors.lastname: Suwa
authors.affiliation: Phyloinformatics Unit, RIKEN Center for Life Science Technologies, 2-2-3 Minatojima-minami, Kobe 650-0047, Japan.
authors.forename: Osamu
authors.initials: O
authors.lastname: Nishimura
authors.affiliation: Department of Biomedical Chemistry, School of Science and Technology, Kwansei Gakuin University, 2-1, Gakuen, Sanda, Hyogo 669-1337, Japan.
authors.forename: Nao
authors.initials: N
authors.lastname: Sakashita
authors.affiliation: Phyloinformatics Unit, RIKEN Center for Life Science Technologies, 2-2-3 Minatojima-minami, Kobe 650-0047, Japan.
authors.forename: Mitsutaka
authors.initials: M
authors.lastname: Kadota
authors.affiliation: Department of Stem Cell Biology and Medicine, Graduate School of Medical Science, Kyushu University, Fukuoka 812-8582, Japan.
authors.forename: Go
authors.initials: G
authors.lastname: Nagamatsu
authors.affiliation: Department of Biomedical Chemistry, School of Science and Technology, Kwansei Gakuin University, 2-1, Gakuen, Sanda, Hyogo 669-1337, Japan.
authors.forename: Masanori
authors.initials: M
authors.lastname: Kawaguchi
authors.affiliation: Department of Biomedical Chemistry, School of Science and Technology, Kwansei Gakuin University, 2-1, Gakuen, Sanda, Hyogo 669-1337, Japan.
authors.forename: Hiroki
authors.initials: H
authors.lastname: Kashida
authors.affiliation: Department of Biomedical Chemistry, School of Science and Technology, Kwansei Gakuin University, 2-1, Gakuen, Sanda, Hyogo 669-1337, Japan.
authors.forename: Ayaka
authors.initials: A
authors.lastname: Nakajima
authors.affiliation: Department of Enzyme Chemistry, Institute for Enzyme Research, Tokushima University, Tokushima 770-8503, Japan.
authors.forename: Makoto
authors.initials: M
authors.lastname: Tachibana
authors.affiliation: Department of Biomedical Chemistry, School of Science and Technology, Kwansei Gakuin University, 2-1, Gakuen, Sanda, Hyogo 669-1337, Japan. Electronic address: yseki@kwansei.ac.jp.
authors.forename: Yoshiyuki
authors.initials: Y
authors.lastname: Seki
mesh_terms: D000818:Animals; D019175:DNA Methylation / Q000235:genetics*; D004268:DNA-Binding Proteins / Q000378:metabolism; D049308:Dioxygenases; D004742:Enhancer Elements, Genetic / Q000235:genetics; D005260:Female; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D005855:Germ Layers / Q000166:cytology; D051741:Kruppel-Like Transcription Factors / Q000378:metabolism; D051379:Mice; D008819:Mice, Nude; D008954:Models, Biological; D000066450:Mouse Embryonic Stem Cells / Q000166:cytology / Q000378:metabolism; D050814:Octamer Transcription Factor-3 / Q000378:metabolism*; D039904:Pluripotent Stem Cells / Q000166:cytology* / Q000378:metabolism*; D011518:Proto-Oncogene Proteins / Q000378:metabolism; D016601:RNA-Binding Proteins; D014157:Transcription Factors / Q000378:metabolism*
chemical_list: D004268:DNA-Binding Proteins; D051741:Kruppel-Like Transcription Factors; D050814:Octamer Transcription Factor-3; C531066:Prdm14 protein, mouse; D011518:Proto-Oncogene Proteins; D016601:RNA-Binding Proteins; C540839:TET1 protein, mouse; D014157:Transcription Factors; D049308:Dioxygenases; C551914:Tet2 protein, mouse
keywords: DNA methylation; embryonic stem cells; epiblast; epigenetics; pluripotency; primordial germ cells; reprogramming