Identification of Enhancers and Transcription Factors Regulating Postnatal Growth of Skeletal Muscle in Cattle

Skeletal muscle undergoes extensive developmental and functional changes during the transition from neonatal to adult stages, but the biological processes and regulatory mechanisms underlying these changes remain incompletely understood. In this study, we integrated RNA-seq and H3K27ac ChIP-seq analyses to characterize transcriptional and epigenomic changes during muscle maturation in neonatal and adult Angus-cross cattle. RNA-seq analysis of longissimus muscle identified 2785 differentially expressed genes (DEGs) between neonatal and adult muscles. Adult muscle showed increased expression of genes associated with muscle maturation, whereas neonatal muscle exhibited higher activity of pathways related to energy metabolism and protein translation. H3K27ac profiling revealed extensive remodeling of active regulatory elements during muscle maturation, including stage-specific enhancers and super-enhancers. Motif enrichment analysis indicated distinct transcription factor networks associated with neonatal- and adult-specific regulatory landscapes. Neonatal muscle-specific enhancers were enriched for motifs of myogenic regulators, including MYOD1, MYOG, SIX family members, and ASCL2, whereas adult muscle-specific enhancers showed increased enrichment of the MEF2 family members. Integration of transcriptomic and epigenomic datasets identified stage-specific enhancers associated with genes involved in neonatal and adult muscle functions. Together, these findings demonstrate that the transition from neonatal to adult muscle is accompanied by coordinated changes in transcriptional programs and enhancer landscapes, providing new insights into the regulatory mechanisms underlying skeletal muscle maturation.