Insulin-like growth factor II (IGF-II) plays a critical role in muscle development, regeneration, and maintenance, yet the mechanisms regulating its muscle-specific expression remain poorly understood. This study examined IGF-II gene regulation during myogenic differentiation of mouse mesenchymal stem cells and myoblasts. IGF-II expression was induced during differentiation and driven exclusively by promoter 3, correlating with increased transcriptional activity. A conserved distal enhancer region within the IGF-II/H19 locus was identified that strongly activated IGF-II promoter 3 during muscle differentiation. These findings advance understanding of IGF-II regulation and identify a key enhancer involved in myogenesis.
