The Evolutionarily Conserved TPM1 Super-Enhancer Drives Skeletal Muscle Regeneration via Mechanotransduction Signaling.

ABSTRACT: Super-enhancers (SEs) are critical epigenetic regulators of tissue regeneration, yet their interplay with cellular biomechanics during myogenic differentiation remains unexplored. Here, the TPM1 locus, encoding a core actin-stabilizing protein essential for skeletal muscle regeneration, harbors an evolutionarily conserved SE (TPM1_SE) that may bridge epigenetic control and mechanotransduction. In vitro, TPM1_SE deletion impaired myogenic differentiation and diminished expression of both TPM1 and its circular RNA (circRNA) isoform, CircTPM1. Conditional deletion of TPM1_SE significantly reduce muscle mass and delayed regenerative progression. Mechanistically, TPM1_SE drives expression of linear TPM1 mRNA (mice) and CircTPM1 (bovine) via TEAD4-mediated chromatin looping, coordinating cytoske

SUBMITTER: Zhang R 

PROVIDER: S-EPMC12915160 | biostudies-literature | 2026 Feb

REPOSITORIES: biostudies-literature