Journal Article

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

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

2013

Overview

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. Surani and colleagues use single-cell transcriptomics analysis in a model of mouse primordial germ cell specification to analyse the collaboration between three transcription factors, BLIMP1, PRDM14 and AP2γ, in determining germ cell fate. They find that BLIMP1 binds directly to repress somatic and cell proliferation genes, and at the same time induces AP2γ, which acts together with PRDM14. The three factors are sufficient for specification and form a tripartite interdependent transcriptional network.

• Publisher: Nature Publishing Group UK,Nature Publishing Group
• Subject: 631/136 / Analysis / Animals / Cancer Research / Cell Biology / Cell Differentiation / Cell Line, Tumor / Cell Proliferation / Cells, Cultured / Developmental Biology / DNA-Binding Proteins / Epigenetics / Gene Expression Regulation, Developmental / Germ cells / Germ Cells - cytology / Germ Cells - metabolism / Life Sciences / Medical research / Mice / Physiological aspects / Positive Regulatory Domain I-Binding Factor 1 / Protein Binding / Repressor Proteins - metabolism / RNA-Binding Proteins / Stem Cells / Tennis / Transcription Factor AP-2 - metabolism / Transcription factors / Transcription Factors - metabolism