title: PRDM14 ensures naive pluripotency through dual regulation of signaling and epigenetic pathways in mouse embryonic stem cells.
abstract: In serum, mouse embryonic stem cells (mESCs) fluctuate between a naive inner cell mass (ICM)-like state and a primed epiblast-like state, but when cultured with inhibitors of the mitogen-activated protein kinase (MAPK) and glycogen synthase kinase 3 pathways (2i), they are harnessed exclusively in a distinct naive pluropotent state, the ground state, that more faithfully recapitulates the ICM. Understanding the mechanism underlying this naive pluripotent state will be critical for realizing the full potential of ESCs. We show here that PRDM14, a PR-domain-containing transcriptional regulator, ensures naive pluripotency through a dual mechanism: antagonizing activation of the fibroblast growth factor receptor (FGFR) signaling by the core pluripotency transcriptional circuitry, and repressing expression of de novo DNA methyltransferases that modify the epigenome to a primed epiblast-like state. PRDM14 exerts these effects by recruiting polycomb repressive complex 2 (PRC2) specifically to key targets and repressing their expression.
authors: Department of Anatomy and Cell Biology, Graduate School of Medicine, Kyoto University, Yoshida-Konoe-cho, Sakyo-ku, Kyoto 606-8501, Japan.
authors: Masashi
authors: M
authors: Yamaji
authors: Jun
authors: J
authors: Ueda
authors: Katsuhiko
authors: K
authors: Hayashi
authors: Hiroshi
authors: H
authors: Ohta
authors: Yukihiro
authors: Y
authors: Yabuta
authors: Kazuki
authors: K
authors: Kurimoto
authors: Ryuichiro
authors: R
authors: Nakato
authors: Yasuhiro
authors: Y
authors: Yamada
authors: Katsuhiko
authors: K
authors: Shirahige
authors: Mitinori
authors: M
authors: Saitou
mesh_terms: D000818:Animals; D047369:Chromatin Immunoprecipitation; D004268:DNA-Binding Proteins; D053595:Embryonic Stem Cells / Q000166:cytology* / Q000378:metabolism*; D057890:Epigenomics; D051379:Mice; D020411:Oligonucleotide Array Sequence Analysis; D063151:Polycomb Repressive Complex 2 / Q000378:metabolism; D011485:Protein Binding; D016601:RNA-Binding Proteins; D017468:Receptors, Fibroblast Growth Factor / Q000378:metabolism; D015398:Signal Transduction / Q000235:genetics / Q000502:physiology*; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*
chemical_list: D004268:DNA-Binding Proteins; C531066:Prdm14 protein, mouse; D016601:RNA-Binding Proteins; D017468:Receptors, Fibroblast Growth Factor; D014157:Transcription Factors; D063151:Polycomb Repressive Complex 2