TY - JOUR
T1 - A tripartite transcription factor network regulates primordial germ cell specification in mice
AU - Magnúsdóttir, Erna
AU - Dietmann, Sabine
AU - Murakami, Kazuhiro
AU - Günesdogan, Ufuk
AU - Tang, Fuchou
AU - Bao, Siqin
AU - Diamanti, Evangelia
AU - Lao, Kaiqin
AU - Gottgens, Berthold
AU - Surani, M. Azim
N1 - 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.
PY - 2013/8
Y1 - 2013/8
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=84881478692&partnerID=8YFLogxK
U2 - 10.1038/ncb2798
DO - 10.1038/ncb2798
M3 - Article
C2 - 23851488
AN - SCOPUS:84881478692
SN - 1465-7392
VL - 15
SP - 905
EP - 915
JO - Nature Cell Biology
JF - Nature Cell Biology
IS - 8
ER -