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The Fgf/Erf/NCoR1/2 repressive axis controls trophoblast cell fate

Author

Listed:
  • Andreas Lackner

    (Medical University of Vienna)

  • Michael Müller

    (Medical University of Vienna)

  • Magdalena Gamperl

    (Medical University of Vienna)

  • Delyana Stoeva

    (Medical University of Vienna)

  • Olivia Langmann

    (Medical University of Vienna)

  • Henrieta Papuchova

    (Medical University of Vienna)

  • Elisabeth Roitinger

    (Institute of Molecular Pathology)

  • Gerhard Dürnberger

    (Institute of Molecular Pathology)

  • Richard Imre

    (Institute of Molecular Pathology)

  • Karl Mechtler

    (Institute of Molecular Pathology)

  • Paulina A. Latos

    (Medical University of Vienna)

Abstract

Placental development relies on coordinated cell fate decisions governed by signalling inputs. However, little is known about how signalling cues are transformed into repressive mechanisms triggering lineage-specific transcriptional signatures. Here, we demonstrate that upon inhibition of the Fgf/Erk pathway in mouse trophoblast stem cells (TSCs), the Ets2 repressor factor (Erf) interacts with the Nuclear Receptor Co-Repressor Complex 1 and 2 (NCoR1/2) and recruits it to key trophoblast genes. Genetic ablation of Erf or Tbl1x (a component of the NCoR1/2 complex) abrogates the Erf/NCoR1/2 interaction. This leads to mis-expression of Erf/NCoR1/2 target genes, resulting in a TSC differentiation defect. Mechanistically, Erf regulates expression of these genes by recruiting the NCoR1/2 complex and decommissioning their H3K27ac-dependent enhancers. Our findings uncover how the Fgf/Erf/NCoR1/2 repressive axis governs cell fate and placental development, providing a paradigm for Fgf-mediated transcriptional control.

Suggested Citation

  • 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.
    • Handle: RePEc:nat:natcom:v:14:y:2023:i:1:d:10.1038_s41467-023-38101-8
    DOI: 10.1038/s41467-023-38101-8
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