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

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/Er...

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Autores principales: Lackner, Andreas, Müller, Michael, Gamperl, Magdalena, Stoeva, Delyana, Langmann, Olivia, Papuchova, Henrieta, Roitinger, Elisabeth, Dürnberger, Gerhard, Imre, Richard, Mechtler, Karl, Latos, Paulina A.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2023
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Article
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10193302/
https://www.ncbi.nlm.nih.gov/pubmed/37137875
http://dx.doi.org/10.1038/s41467-023-38101-8
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author Lackner, Andreas
Müller, Michael
Gamperl, Magdalena
Stoeva, Delyana
Langmann, Olivia
Papuchova, Henrieta
Roitinger, Elisabeth
Dürnberger, Gerhard
Imre, Richard
Mechtler, Karl
Latos, Paulina A.
author_facet Lackner, Andreas
Müller, Michael
Gamperl, Magdalena
Stoeva, Delyana
Langmann, Olivia
Papuchova, Henrieta
Roitinger, Elisabeth
Dürnberger, Gerhard
Imre, Richard
Mechtler, Karl
Latos, Paulina A.
author_sort Lackner, Andreas
collection PubMed
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 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.
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spelling pubmed-101933022023-05-19 The Fgf/Erf/NCoR1/2 repressive axis controls trophoblast cell fate Lackner, Andreas Müller, Michael Gamperl, Magdalena Stoeva, Delyana Langmann, Olivia Papuchova, Henrieta Roitinger, Elisabeth Dürnberger, Gerhard Imre, Richard Mechtler, Karl Latos, Paulina A. Nat Commun Article 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. Nature Publishing Group UK 2023-05-04 /pmc/articles/PMC10193302/ /pubmed/37137875 http://dx.doi.org/10.1038/s41467-023-38101-8 Text en © The Author(s) 2023 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Article
Lackner, Andreas
Müller, Michael
Gamperl, Magdalena
Stoeva, Delyana
Langmann, Olivia
Papuchova, Henrieta
Roitinger, Elisabeth
Dürnberger, Gerhard
Imre, Richard
Mechtler, Karl
Latos, Paulina A.
The Fgf/Erf/NCoR1/2 repressive axis controls trophoblast cell fate
title The Fgf/Erf/NCoR1/2 repressive axis controls trophoblast cell fate
title_full The Fgf/Erf/NCoR1/2 repressive axis controls trophoblast cell fate
title_fullStr The Fgf/Erf/NCoR1/2 repressive axis controls trophoblast cell fate
title_full_unstemmed The Fgf/Erf/NCoR1/2 repressive axis controls trophoblast cell fate
title_short The Fgf/Erf/NCoR1/2 repressive axis controls trophoblast cell fate
title_sort fgf/erf/ncor1/2 repressive axis controls trophoblast cell fate
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10193302/
https://www.ncbi.nlm.nih.gov/pubmed/37137875
http://dx.doi.org/10.1038/s41467-023-38101-8
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