Multi-Omics Epigenetic Landscape Unveils Regulatory Mechanisms Underlying Heterosis in Sheep Muscle Development

Area of Science:

• Animal Genetics and Genomics
• Epigenetics and Gene Regulation
• Livestock Breeding and Production

Background:

• Hybridization significantly improves sheep productivity, but the underlying epigenetic mechanisms are not well understood.
• Understanding these mechanisms is crucial for optimizing breeding strategies and enhancing livestock performance.

Purpose of the Study:

• To investigate the epigenetic regulatory differences in muscle tissue between Hu sheep (HU) and their crossbred progeny with Suffolk rams (SH).
• To identify candidate genes and regulatory elements associated with the superior growth and muscle development observed in crossbred sheep.

Main Methods:

• Integrated multi-omics approaches: RNA-seq, ATAC-seq, and CUT&Tag (H3K4me3, H3K4me1, H3K27ac, H3K27me3).
• Hidden Markov Model for chromatin state annotation.
• Motif analysis of enhancer elements.
• Construction of a putative regulatory network.

Main Results:

• SH crossbred sheep showed superior growth performance and increased eye muscle area, correlated with upregulated Apelin signaling pathway genes.
• HU sheep exhibited enrichment of repressive H3K27me3 modifications, while SH sheep had enriched active enhancers (EnhA) linked to upregulated genes.
• Identified 1862 SH-specific and 691 HU-specific EnhA elements, with SH-specific enhancers enriched for myogenic MEF2 motifs.
• Discovered a regulatory network implicating CMKLR1, PPARGC1A, and TLE3 as core hub genes.

Conclusions:

• Epigenomic differences, particularly enhancer activity and repressive marks, contribute to superior muscle phenotypes in crossbred sheep.
• SH-specific enhancers and associated myogenic transcription factors play a significant role in muscle and vascular development.
• This study provides valuable insights and candidate genes for improving sheep breeding programs through epigenetic understanding.