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

Erna Magnúsdóttir, Sabine Dietmann, Kazuhiro Murakami, Ufuk Günesdogan, Fuchou Tang, Siqin Bao, Evangelia Diamanti, Kaiqin Lao, Berthold Gottgens, M. Azim Surani*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

164 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)905-915
Number of pages11
JournalNature Cell Biology
Volume15
Issue number8
DOIs
Publication statusPublished - Aug 2013

Bibliographical note

Funding Information:
We thank N. Miller for flow cytometry, and M. Trotter, C. Bradshaw and G. Allen for bioinformatics analysis. We thank S. Kim for help with figures. We thank R. Sen-gupta and J. Hackett for critically reading the manuscript. This work was supported by grants from the Wellcome Trust and HFSP to M.A.S. and the ERC to E.M.

Fingerprint

Dive into the research topics of 'A tripartite transcription factor network regulates primordial germ cell specification in mice'. Together they form a unique fingerprint.

Cite this