Nature Research, Nature Cell Biology, 8(15), p. 905-915, 2013
DOI: 10.1038/ncb2798
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Transitions in cell states are controlled by combinatorial actions of transcription factors. For primordial germ cell (PGC) specification, BLIMP1 the key regulator 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 ChIPseq 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 with BLIMP1 and PRDM14, 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.