Hybridization effectively enhances breeding efficiency and significantly boosts sheep productivity. However, the epigenetic mechanisms underlying the superior production performance of crossbreds remain largely elusive. In this study, Hu sheep were crossbred with Suffolk rams used as the paternal line. We integrated RNA-seq, ATAC-seq, and CUT&Tag (H3K4me3, H3K4me1, H3K27ac, and H3K27me3) techniques to characterize epigenetic regulatory differences in the longissimus dorsi muscle between Hu sheep (HU) and crossbred progeny (SH). Phenotypic and transcriptomic analyses revealed that SH crossbred sheep exhibited superior growth performance (p < 0.05), and the upregulated genes in the Apelin signaling pathway were significantly correlated with eye muscle area (p < 0.05). Utilizing a Hidden Markov Model, we annotated 15 distinct chromatin states in both HU and SH sheep, systematically characterizing the dynamic epigenomic landscapes across the two breeds. In contrast to SH sheep, the genome of HU sheep exhibited enrichment of repressive chromatin modifications typified by H3K27me3. Strong active enhancers (EnhA) were significantly enriched within upregulated genes in SH. A total of 1862 SH-specific and 691 HU-specific EnhA elements were characterized in this study. Motif analysis revealed that SH-specific EnhA were enriched for myogenic MEF2 family motifs (p < 0.05), which promote muscle and vascular development. By integrating multi-omics data, we constructed a putative regulatory network potentially modulated by SH-specific enhancers, identifying CMKLR1, PPARGC1A, and TLE3 as the core hub genes. Collectively, this study provides a robust data resource, identifying candidate genes and regulatory elements associated with crossbreeding-related muscle phenotypes.
Cheng et al. (Sat,) studied this question.