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Reprogramming of cis-regulatory networks during skeletal muscle atrophy in male mice

A comprehensive atlas of cis-regulatory elements and their dynamic activity is necessary to understand the transcriptional basis of cellular structure maintenance, metabolism, and responses to the environment. Here we show, using matched single-nucleus chromatin accessibility and RNA-sequencing from...

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Autores principales: Lin, Hongchun, Peng, Hui, Sun, Yuxiang, Si, Meijun, Wu, Jiao, Wang, Yanlin, Thomas, Sandhya S., Sun, Zheng, Hu, Zhaoyong
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10584982/
https://www.ncbi.nlm.nih.gov/pubmed/37853001
http://dx.doi.org/10.1038/s41467-023-42313-3
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author Lin, Hongchun
Peng, Hui
Sun, Yuxiang
Si, Meijun
Wu, Jiao
Wang, Yanlin
Thomas, Sandhya S.
Sun, Zheng
Hu, Zhaoyong
author_facet Lin, Hongchun
Peng, Hui
Sun, Yuxiang
Si, Meijun
Wu, Jiao
Wang, Yanlin
Thomas, Sandhya S.
Sun, Zheng
Hu, Zhaoyong
author_sort Lin, Hongchun
collection PubMed
description A comprehensive atlas of cis-regulatory elements and their dynamic activity is necessary to understand the transcriptional basis of cellular structure maintenance, metabolism, and responses to the environment. Here we show, using matched single-nucleus chromatin accessibility and RNA-sequencing from juvenile male C57BL6 mice, an atlas of accessible chromatin regions in both normal and denervated skeletal muscles. We identified cell-type-specific cis-regulatory networks, highlighting the dynamic regulatory circuits mediating transitions between myonuclear types. Through comparison of normal and perturbed muscle, we delineated the reprogramming of cis-regulatory networks in response to denervation, described the interplay of promoters/enhancers and target genes. We further unveil a hierarchical structure of transcription factors that delineate a regulatory network in atrophic muscle, identifying ELK4 as a key atrophy-related transcription factor that instigates muscle atrophy through TGF-β1 regulation. This study furnishes a rich genomic resource, essential for decoding the regulatory dynamics of skeletal muscle in both physiological and pathological states.
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spelling pubmed-105849822023-10-20 Reprogramming of cis-regulatory networks during skeletal muscle atrophy in male mice Lin, Hongchun Peng, Hui Sun, Yuxiang Si, Meijun Wu, Jiao Wang, Yanlin Thomas, Sandhya S. Sun, Zheng Hu, Zhaoyong Nat Commun Article A comprehensive atlas of cis-regulatory elements and their dynamic activity is necessary to understand the transcriptional basis of cellular structure maintenance, metabolism, and responses to the environment. Here we show, using matched single-nucleus chromatin accessibility and RNA-sequencing from juvenile male C57BL6 mice, an atlas of accessible chromatin regions in both normal and denervated skeletal muscles. We identified cell-type-specific cis-regulatory networks, highlighting the dynamic regulatory circuits mediating transitions between myonuclear types. Through comparison of normal and perturbed muscle, we delineated the reprogramming of cis-regulatory networks in response to denervation, described the interplay of promoters/enhancers and target genes. We further unveil a hierarchical structure of transcription factors that delineate a regulatory network in atrophic muscle, identifying ELK4 as a key atrophy-related transcription factor that instigates muscle atrophy through TGF-β1 regulation. This study furnishes a rich genomic resource, essential for decoding the regulatory dynamics of skeletal muscle in both physiological and pathological states. Nature Publishing Group UK 2023-10-18 /pmc/articles/PMC10584982/ /pubmed/37853001 http://dx.doi.org/10.1038/s41467-023-42313-3 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 licence, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence 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 licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Article
Lin, Hongchun
Peng, Hui
Sun, Yuxiang
Si, Meijun
Wu, Jiao
Wang, Yanlin
Thomas, Sandhya S.
Sun, Zheng
Hu, Zhaoyong
Reprogramming of cis-regulatory networks during skeletal muscle atrophy in male mice
title Reprogramming of cis-regulatory networks during skeletal muscle atrophy in male mice
title_full Reprogramming of cis-regulatory networks during skeletal muscle atrophy in male mice
title_fullStr Reprogramming of cis-regulatory networks during skeletal muscle atrophy in male mice
title_full_unstemmed Reprogramming of cis-regulatory networks during skeletal muscle atrophy in male mice
title_short Reprogramming of cis-regulatory networks during skeletal muscle atrophy in male mice
title_sort reprogramming of cis-regulatory networks during skeletal muscle atrophy in male mice
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10584982/
https://www.ncbi.nlm.nih.gov/pubmed/37853001
http://dx.doi.org/10.1038/s41467-023-42313-3
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