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

ABSTRACT: Here, we demonstrate that upon inhibition of the Fgf/Erk pathway in mouse trophoblast stem cells (TSCs), the Ets2 repressor factor (Erf) interacts with components of the Nuclear Receptor Corepressor Complex 1 and 2 (NCoR1 and NCoR2). Upon attenuation of Fgf signalling, unphosphorylated, nuclear Erf recruits the NCoR1/2 complex to key trophoblast genes, brings about their transcriptional silencing and facilitates differentiation and placental development.

INSTRUMENT(S): Orbitrap Fusion Lumos, Q Exactive HF, Q Exactive

ORGANISM(S): Mus Musculus (mouse)

TISSUE(S): Trophoblast Stem Cell

SUBMITTER: Richard Imre

LAB HEAD: Paulina A. Latos

PROVIDER: PXD037892 | Pride | 2023-04-26

REPOSITORIES: Pride

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

Project description:Placental development relies on coordinated cell fate decisions governed by signalling inputs. However, little is known about how signalling cues are transformed into repressive 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 Corepressor 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 to their enhancers and modulation of H3K27ac. Our findings uncover how the Fgf/Erf/NCoR1/2 repressive axis governs cell fate and placental development, providing a new paradigm for Fgf-mediated transcriptional control.

2023-04-26 | GSE199024 | GEO

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