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Publication : A tripartite transcription factor network regulates primordial germ cell specification in mice.

First Author  Magnúsdóttir E Year  2013
Journal  Nat Cell Biol Volume  15
Issue  8 Pages  905-15
PubMed ID  23851488 Mgi Jnum  J:201514
Mgi Id  MGI:5514282 Doi  10.1038/ncb2798
Citation  Magnusdottir E, et al. (2013) A tripartite transcription factor network regulates primordial germ cell specification in mice. Nat Cell Biol 15(8):905-15
abstractText  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 AP2gamma. 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 AP2gamma, which together with PRDM14 initiates the PGC-specific fate. We determined the occupancy of critical genes by AP2gamma-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, AP2gamma and PRDM14 are sufficient for PGC specification, and the unprecedented resetting of the epigenome towards a basal state.
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