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

Author

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  • Paulina A. Latos

    (Epigenetics Programme, The Babraham Institute, Babraham Research Campus
    Centre for Trophoblast Research, University of Cambridge)

  • 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
    Medical Research Council Biostatistics Unit, Cambridge Institute of Public Health, Robinson Way)

  • Myriam Hemberger

    (Epigenetics Programme, The Babraham Institute, Babraham Research Campus
    Centre for Trophoblast Research, University of Cambridge)

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.

Suggested Citation

  • Paulina A. Latos & Angela Goncalves & David Oxley & Hisham Mohammed & Ernest Turro & Myriam Hemberger, 2015. "Fgf and Esrrb integrate epigenetic and transcriptional networks that regulate self-renewal of trophoblast stem cells," Nature Communications, Nature, vol. 6(1), pages 1-14, November.
    • Handle: RePEc:nat:natcom:v:6:y:2015:i:1:d:10.1038_ncomms8776
    DOI: 10.1038/ncomms8776
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    Cited by:

    1. Kaela M. Varberg & Esteban M. Dominguez & Boryana Koseva & Joseph M. Varberg & Ross P. McNally & Ayelen Moreno-Irusta & Emily R. Wesley & Khursheed Iqbal & Warren A. Cheung & Carl Schwendinger-Schreck, 2023. "Extravillous trophoblast cell lineage development is associated with active remodeling of the chromatin landscape," Nature Communications, Nature, vol. 14(1), pages 1-23, December.
    2. Moriyah Naama & Moran Rahamim & Valery Zayat & Shulamit Sebban & Ahmed Radwan & Dana Orzech & Rachel Lasry & Annael Ifrah & Mohammad Jaber & Ofra Sabag & Hazar Yassen & Areej Khatib & Silvina Epsztejn, 2023. "Pluripotency-independent induction of human trophoblast stem cells from fibroblasts," Nature Communications, Nature, vol. 14(1), pages 1-22, December.
    3. Andreas Lackner & Michael Müller & Magdalena Gamperl & Delyana Stoeva & Olivia Langmann & Henrieta Papuchova & Elisabeth Roitinger & Gerhard Dürnberger & Richard Imre & Karl Mechtler & Paulina A. Lato, 2023. "The Fgf/Erf/NCoR1/2 repressive axis controls trophoblast cell fate," Nature Communications, Nature, vol. 14(1), pages 1-20, December.

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