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

First Author  Lin H Year  2023
Journal  Nat Commun Volume  14
Issue  1 Pages  6581
PubMed ID  37853001 Mgi Jnum  J:357231
Mgi Id  MGI:7542357 Doi  10.1038/s41467-023-42313-3
Citation  Lin H, et al. (2023) Reprogramming of cis-regulatory networks during skeletal muscle atrophy in male mice. Nat Commun 14(1):6581
abstractText  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-beta1 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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