title: A tripartite transcription factor network regulates primordial germ cell specification in mice.
abstract: Transitions in cell states are controlled by combinatorial actions of transcription factors. BLIMP1, the key regulator of primordial germ cell (PGC) specification, apparently acts together with PRDM14 and AP2γ. To investigate their individual and combinatorial functions, we first sought an in vitro system for transcriptional readouts and chromatin immunoprecipitation sequencing analysis. We then integrated this data with information from single-cell transcriptome analysis of normal and mutant PGCs. Here we show that BLIMP1 binds directly to repress somatic and cell proliferation genes. It also directly induces AP2γ, which together with PRDM14 initiates the PGC-specific fate. We determined the occupancy of critical genes by AP2γ-which, when computed altogether with those of BLIMP1 and PRDM14 (both individually and cooperatively), reveals a tripartite mutually interdependent transcriptional network for PGCs. We also demonstrate that, in principle, BLIMP1, AP2γ and PRDM14 are sufficient for PGC specification, and the unprecedented resetting of the epigenome towards a basal state.
authors.affiliation: Wellcome Trust/Cancer Research UK Gurdon Institute, University of Cambridge, Tennis Court Road, Cambridge CB2 1QN, UK.
authors.forename: Erna
authors.initials: E
authors.lastname: Magnúsdóttir
authors.forename: Sabine
authors.initials: S
authors.lastname: Dietmann
authors.forename: Kazuhiro
authors.initials: K
authors.lastname: Murakami
authors.forename: Ufuk
authors.initials: U
authors.lastname: Günesdogan
authors.forename: Fuchou
authors.initials: F
authors.lastname: Tang
authors.forename: Siqin
authors.initials: S
authors.lastname: Bao
authors.forename: Evangelia
authors.initials: E
authors.lastname: Diamanti
authors.forename: Kaiqin
authors.initials: K
authors.lastname: Lao
authors.forename: Berthold
authors.initials: B
authors.lastname: Gottgens
authors.forename: M
authors.initials: M
authors.lastname: Azim Surani
mesh_terms: D000818:Animals; D002454:Cell Differentiation; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D002478:Cells, Cultured; D004268:DNA-Binding Proteins; D018507:Gene Expression Regulation, Developmental; D005854:Germ Cells / Q000166:cytology* / Q000378:metabolism*; D051379:Mice; D000074462:Positive Regulatory Domain I-Binding Factor 1; D011485:Protein Binding; D016601:RNA-Binding Proteins; D012097:Repressor Proteins / Q000378:metabolism; D050656:Transcription Factor AP-2 / Q000378:metabolism; D014157:Transcription Factors / Q000378:metabolism*
chemical_list: D004268:DNA-Binding Proteins; C524724:PRDM14 protein, human; D016601:RNA-Binding Proteins; D012097:Repressor Proteins; D050656:Transcription Factor AP-2; D014157:Transcription Factors; C087042:PRDM1 protein, human; D000074462:Positive Regulatory Domain I-Binding Factor 1