2. Academic Validation
  3. Fgf and Esrrb integrate epigenetic and transcriptional networks that regulate self-renewal of trophoblast stem cells

Fgf and Esrrb integrate epigenetic and transcriptional networks that regulate self-renewal of trophoblast stem cells

  • Nat Commun. 2015 Jul 24:6:7776. doi: 10.1038/ncomms8776.
Paulina A Latos 1,  Angela Goncalves 2,  David Oxley 3,  Hisham Mohammed 4,  Ernest Turro 5,  Myriam Hemberger 1
Affiliations

Affiliations

  • 1 1] Epigenetics Programme, The Babraham Institute, Babraham Research Campus, Cambridge CB22 3AT, UK [2] Centre for Trophoblast Research, University of Cambridge, Downing Street, Cambridge CB2 3EG, UK.
  • 2 Wellcome Trust Sanger Institute, Cambridge CB10 1SA, UK.
  • 3 Proteomics Group, The Babraham Institute, Babraham Research Campus, Cambridge CB22 3AT, UK.
  • 4 Epigenetics Programme, The Babraham Institute, Babraham Research Campus, Cambridge CB22 3AT, UK.
  • 5 1] Department of Haematology, University of Cambridge, NHS Blood and Transplant, Long Road, Cambridge CB2 0PT, UK [2] Medical Research Council Biostatistics Unit, Cambridge Institute of Public Health, Robinson Way, Forvie Site, Cambridge CB2 0SR, UK.
PMID: 26206133 DOI: 10.1038/ncomms8776
Abstract

Esrrb (oestrogen-related receptor beta) is a transcription factor implicated in embryonic stem (ES) cell self-renewal, yet its knockout causes intrauterine lethality due to defects in trophoblast development. Here we show that in trophoblast stem (TS) cells, Esrrb is a downstream target of Fibroblast Growth Factor (Fgf) signalling and is critical to drive TS cell self-renewal. In contrast to its occupancy of pluripotency-associated loci in ES cells, Esrrb sustains the stemness of TS cells by direct binding and regulation of TS cell-specific transcription factors including Elf5 and Eomes. To elucidate the mechanisms whereby Esrrb controls the expression of its targets, we characterized its TS cell-specific interactome using mass spectrometry. Unlike in ES cells, Esrrb interacts in TS cells with the Histone Demethylase Lsd1 and with the RNA Polymerase II-associated Integrator complex. Our findings provide new insights into both the general and context-dependent wiring of transcription factor networks in stem cells by master transcription factors.

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