Intermittent AP-1 activation in muscles contributes to exercise-induced health benefits.

ABSTRACT: Regular physical exercise extends healthspan, yet the molecular mechanisms that translate intermittent contractile stress into lasting benefit remain incompletely understood. Using global nuclear run-on (GRO-seq) in mouse skeletal muscle after treadmill running, we profiled enhancer RNA (eRNA), a sensitive marker of enhancer activity. Activation protein-1 (AP-1), a family of pioneering factors for senescence, emerged as the top transcription factor with motif enrichment in exercise-activated enhancers. Our screen in the contracting C2C12 myotubes pinpointed cFos/JunD as the primary AP-1 factor responsible for contraction-induced transcriptional changes. Muscle-specific overexpression of A-Fos, a dominant-negative mutant of cFos, disrupted transcriptomic responses to exercise and attenuated

SUBMITTER: Choubey A 

PROVIDER: S-EPMC12803081 | biostudies-literature | 2026 Jan

REPOSITORIES: biostudies-literature