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

Paulina A. Latos (), Angela Goncalves, David Oxley, Hisham Mohammed, Ernest Turro and Myriam Hemberger ()
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Paulina A. Latos: Epigenetics Programme, The Babraham Institute, Babraham Research Campus
Angela Goncalves: Wellcome Trust Sanger Institute
David Oxley: Proteomics Group, The Babraham Institute, Babraham Research Campus
Hisham Mohammed: Epigenetics Programme, The Babraham Institute, Babraham Research Campus
Ernest Turro: University of Cambridge, NHS Blood and Transplant
Myriam Hemberger: Epigenetics Programme, The Babraham Institute, Babraham Research Campus

Nature Communications, 2015, vol. 6, issue 1, 1-14

Abstract: 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.

Date: 2015
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DOI: 10.1038/ncomms8776

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