Endurance training promotes chromatin closure and timely repression of the post-exercise immediate early stress response [ATAC-seq]

Methods: A multi-omics analysis was performed: ATAC-sequencing was used to map chromatin accessibility in myonuclei isolated from endurance-trained and untrained mice at multiple time points (0h, 6h, and 72h) post-exercise. Gene expression was assessed via RNA-sequencing, and motif activity analysis identified regulatory factors involved in exercise-induced chromatin remodeling and transcriptomic response. Results: Endurance training amplified rapid chromatin closing immediately after exercise, with trained muscle exhibiting a more pronounced loss of chromatin accessibility at 0h and 6h post-exercise compared to untrained muscle. These chromatin accessibility changes persisted longer in trained muscle, with significant retention until 72h post-exercise. Immediate early transcription factors, such as Fos and Jun, showed a training state-dependent shift in activation dynamics. Similarly, specific modulation of genes involved in metabolism, insulin response and angiogenesis was observed. Conclusions: Endurance training triggers rapid and persistent chromatin remodeling in muscle, contributing to the transcriptional response to exercise. Our findings suggest that training induces long-lasting epigenetic changes, potentially underpinning muscle memory and improved physiological resilience. These new insights into the molecular mechanisms of muscle adaptation help to understand the training response, and might become relevant in disease prevention.