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

Hongchun Lin, Hui Peng (), Yuxiang Sun, Meijun Si, Jiao Wu, Yanlin Wang, Sandhya S. Thomas, Zheng Sun and Zhaoyong Hu ()
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Hongchun Lin: the Third Affiliated Hospital of Sun Yat-sen University
Hui Peng: the Third Affiliated Hospital of Sun Yat-sen University
Yuxiang Sun: the Third Affiliated Hospital of Sun Yat-sen University
Meijun Si: Guangdong Provincial People’s Hospital
Jiao Wu: Baylor College of Medicine
Yanlin Wang: University of Connecticut School of Medicine
Sandhya S. Thomas: Baylor College of Medicine
Zheng Sun: Baylor College of Medicine
Zhaoyong Hu: Baylor College of Medicine

Nature Communications, 2023, vol. 14, issue 1, 1-17

Abstract: Abstract 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.

Date: 2023
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DOI: 10.1038/s41467-023-42313-3

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