Format

Send to

Choose Destination
See comment in PubMed Commons below
Nat Cell Biol. 2013 Aug;15(8):905-15. doi: 10.1038/ncb2798. Epub 2013 Jul 14.

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

Author information

1
Wellcome Trust/Cancer Research UK Gurdon Institute, University of Cambridge, Tennis Court Road, Cambridge CB2 1QN, UK.

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.

PMID:
23851488
PMCID:
PMC3796875
DOI:
10.1038/ncb2798
[Indexed for MEDLINE]
Free PMC Article
PubMed Commons home

PubMed Commons

0 comments
How to join PubMed Commons

    Supplemental Content

    Full text links

    Icon for Nature Publishing Group Icon for PubMed Central
    Loading ...
    Support Center