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


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.

SUBMITTER: Lin H 

PROVIDER: S-EPMC10584982 | biostudies-literature | 2023 Oct

REPOSITORIES: biostudies-literature

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

Lin Hongchun H   Peng Hui H   Sun Yuxiang Y   Si Meijun M   Wu Jiao J   Wang Yanlin Y   Thomas Sandhya S SS   Sun Zheng Z   Hu Zhaoyong Z  

Nature communications 20231018 1


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  ...[more]

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