The atlas of promoter-enhancer interactions during myogenic differentiation offers novel insights into genetic variants related to meat traits in pigs

The lack of knowledge about how the genome is regulated during skeletal myogenesis in pigs hinders the identification of genetic variants for meat traits. Here, we systematically characterized the cis -regulatory elements (CREs, promoters, enhancers and others) by using Hi-C coupled chromatin cleavage and tagmentation (HiCuT, H3K27ac), Assay for transposase-accessible chromatin using sequencing (ATAC-seq) and RNA-seq to analyze primary myoblasts and in vitro well-differentiated myotubes, and generated an atlas of the promoter-enhancer interactions (PEIs) during myogenic differentiation. In total, 179,895 and 159,255 loops were identified in myoblasts and myotubes, respectively, which could be grouped into 3 categories of promoter-promoter interactions, promoter-enhancer interactions and promoter-others. Furthermore, 22,645 cis -eQTLs loci were pinpointed by integrating public genome-wide association studies (GWAS) and expression quantitative trait locus (eQTL) datasets. Notably, novel promoter-like enhancers were verified, and cis -eQTLs in promoter-like enhancers might influence gene expression over a long range. In addition, 39,069 structural variants (SVs) within the CREs were identified. A transcription factor (TF)-promoter/enhancer regulatory network for myogenesis was generated, revealing several novel TFs relevant to myogenic differentiation. This work generated a valuable resource for understanding genomic regulation in pig muscles and filtering potential variants to develop breeds with desirable traits.