KDM5A overexpression modulates key myogenic differentiation factors and sarcomere gene expression

Myogenic differentiation is a complex and tightly regulated process involving multiple transcriptional regulators. KDM5A (lysine demethylase 5A) is a histone demethylase that regulates gene transcription and has been implicated in skeletal muscle differentiation. In Inclusion Body Myositis, we previously associated dysregulated myogenic differentiation with KDM5A overactivity. Immortalised human myoblasts overexpressing KDM5A showed an altered transcriptional landscape, with differential expression of key myogenic differentiation factors and significantly increased expression of sarcomeric genes. Although no morphological differences were observed, KDM5A-overexpressing myotubes showed a higher proportion of myogenin-positive nuclei during late-stage differentiation, suggesting that KDM5A modulates myogenic differentiation dynamics.