Going nuclear: Molecular adaptations to exercise mediated by myonuclei

Muscle fibers are multinucleated, and muscle fiber nuclei (myonuclei) are believed to be post-mitotic and are typically situated near the periphery of the myofiber. Due to the unique organization of muscle fibers and their nuclei, the cellular and molecular mechanisms regulating myofiber homeostasis in unstressed and stressed conditions (e.g., exercise) are unique. A key role myonuclei play in regulating muscle during exercise is gene transcription. Only recently have investigators had the capability to identify molecular changes at high resolution exclusively in myonuclei in response to perturbations in vivo. The purpose of this review is to describe how myonuclei modulate their transcriptome, epigenetic status, mobility and shape, and microRNA expression in response to exercise in vivo. Given the relative paucity of high-fidelity information on myonucleus-specific contributions to exercise adaptation, we identify specific gaps in knowledge and provide perspectives on future directions of research.