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. |