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Myod1 and GR coordinate myofiber-specific transcriptional enhancers

Skeletal muscle is a dynamic tissue the size of which can be remodeled through the concerted actions of various cues. Here, we investigated the skeletal muscle transcriptional program and identified key tissue-specific regulatory genetic elements. Our results show that Myod1 is bound to numerous ske...

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Autores principales: Rovito, Daniela, Rerra, Anna-Isavella, Ueberschlag-Pitiot, Vanessa, Joshi, Shilpy, Karasu, Nezih, Dacleu-Siewe, Vanessa, Rayana, Khalil Ben, Ghaibour, Kamar, Parisotto, Maxime, Ferry, Arnaud, Jelinsky, Scott A, Laverny, Gilles, Klaholz, Bruno P, Sexton, Tom, Billas, Isabelle M L, Duteil, Delphine, Metzger, Daniel
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Oxford University Press 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8096230/
https://www.ncbi.nlm.nih.gov/pubmed/33836079
http://dx.doi.org/10.1093/nar/gkab226
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author Rovito, Daniela
Rerra, Anna-Isavella
Ueberschlag-Pitiot, Vanessa
Joshi, Shilpy
Karasu, Nezih
Dacleu-Siewe, Vanessa
Rayana, Khalil Ben
Ghaibour, Kamar
Parisotto, Maxime
Ferry, Arnaud
Jelinsky, Scott A
Laverny, Gilles
Klaholz, Bruno P
Sexton, Tom
Billas, Isabelle M L
Duteil, Delphine
Metzger, Daniel
author_facet Rovito, Daniela
Rerra, Anna-Isavella
Ueberschlag-Pitiot, Vanessa
Joshi, Shilpy
Karasu, Nezih
Dacleu-Siewe, Vanessa
Rayana, Khalil Ben
Ghaibour, Kamar
Parisotto, Maxime
Ferry, Arnaud
Jelinsky, Scott A
Laverny, Gilles
Klaholz, Bruno P
Sexton, Tom
Billas, Isabelle M L
Duteil, Delphine
Metzger, Daniel
author_sort Rovito, Daniela
collection PubMed
description Skeletal muscle is a dynamic tissue the size of which can be remodeled through the concerted actions of various cues. Here, we investigated the skeletal muscle transcriptional program and identified key tissue-specific regulatory genetic elements. Our results show that Myod1 is bound to numerous skeletal muscle enhancers in collaboration with the glucocorticoid receptor (GR) to control gene expression. Remarkably, transcriptional activation controlled by these factors occurs through direct contacts with the promoter region of target genes, via the CpG-bound transcription factor Nrf1, and the formation of Ctcf-anchored chromatin loops, in a myofiber-specific manner. Moreover, we demonstrate that GR negatively controls muscle mass and strength in mice by down-regulating anabolic pathways. Taken together, our data establish Myod1, GR and Nrf1 as key players of muscle-specific enhancer-promoter communication that orchestrate myofiber size regulation.
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spelling pubmed-80962302021-05-10 Myod1 and GR coordinate myofiber-specific transcriptional enhancers Rovito, Daniela Rerra, Anna-Isavella Ueberschlag-Pitiot, Vanessa Joshi, Shilpy Karasu, Nezih Dacleu-Siewe, Vanessa Rayana, Khalil Ben Ghaibour, Kamar Parisotto, Maxime Ferry, Arnaud Jelinsky, Scott A Laverny, Gilles Klaholz, Bruno P Sexton, Tom Billas, Isabelle M L Duteil, Delphine Metzger, Daniel Nucleic Acids Res Gene regulation, Chromatin and Epigenetics Skeletal muscle is a dynamic tissue the size of which can be remodeled through the concerted actions of various cues. Here, we investigated the skeletal muscle transcriptional program and identified key tissue-specific regulatory genetic elements. Our results show that Myod1 is bound to numerous skeletal muscle enhancers in collaboration with the glucocorticoid receptor (GR) to control gene expression. Remarkably, transcriptional activation controlled by these factors occurs through direct contacts with the promoter region of target genes, via the CpG-bound transcription factor Nrf1, and the formation of Ctcf-anchored chromatin loops, in a myofiber-specific manner. Moreover, we demonstrate that GR negatively controls muscle mass and strength in mice by down-regulating anabolic pathways. Taken together, our data establish Myod1, GR and Nrf1 as key players of muscle-specific enhancer-promoter communication that orchestrate myofiber size regulation. Oxford University Press 2021-04-09 /pmc/articles/PMC8096230/ /pubmed/33836079 http://dx.doi.org/10.1093/nar/gkab226 Text en © The Author(s) 2021. Published by Oxford University Press on behalf of Nucleic Acids Research. https://creativecommons.org/licenses/by-nc/4.0/This is an Open Access article distributed under the terms of the Creative Commons Attribution-NonCommercial License (http://creativecommons.org/licenses/by-nc/4.0/ (https://creativecommons.org/licenses/by-nc/4.0/) ), which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is properly cited. For commercial re-use, please contact journals.permissions@oup.com
spellingShingle Gene regulation, Chromatin and Epigenetics
Rovito, Daniela
Rerra, Anna-Isavella
Ueberschlag-Pitiot, Vanessa
Joshi, Shilpy
Karasu, Nezih
Dacleu-Siewe, Vanessa
Rayana, Khalil Ben
Ghaibour, Kamar
Parisotto, Maxime
Ferry, Arnaud
Jelinsky, Scott A
Laverny, Gilles
Klaholz, Bruno P
Sexton, Tom
Billas, Isabelle M L
Duteil, Delphine
Metzger, Daniel
Myod1 and GR coordinate myofiber-specific transcriptional enhancers
title Myod1 and GR coordinate myofiber-specific transcriptional enhancers
title_full Myod1 and GR coordinate myofiber-specific transcriptional enhancers
title_fullStr Myod1 and GR coordinate myofiber-specific transcriptional enhancers
title_full_unstemmed Myod1 and GR coordinate myofiber-specific transcriptional enhancers
title_short Myod1 and GR coordinate myofiber-specific transcriptional enhancers
title_sort myod1 and gr coordinate myofiber-specific transcriptional enhancers
topic Gene regulation, Chromatin and Epigenetics
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8096230/
https://www.ncbi.nlm.nih.gov/pubmed/33836079
http://dx.doi.org/10.1093/nar/gkab226
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