Allele-specific Effects of Three-dimensional Genome Architecture in Hybrid Pigs

Abstract

In diploid mammals, allele-specific three-dimensional (3D) genome architecture may lead to imbalanced gene expression. Through ultradeep in situ Hi-C sequencing of three representative somatic tissues (liver, skeletal muscle, and brain) from hybrid pigs generated by reciprocal crosses of phenotypically and physiologically divergent Berkshire and Tibetan pigs, we uncover extensive chromatin reorganization between homologous chromosomes across multiple scales. Haplotype-based interrogation of multi-omics data revealed the tissue-dependence of 3D chromatin conformation, suggesting that parent-of-origin-specific conformation may drive gene imprinting. We quantify the effects of genetic variations and histone modifications on allelic rewiring of long-range promoter-enhancer contacts, which likely contribute to the dramatic phenotypic differences between the parental pig breeds. This study also provides definitive evidence of structured homolog pairing in the pig genome which could facilitate regulatory interactions between homologous chromosomes. This work illustrates how allele-specific chromatin architecture facilitates concomitant shifts in allele-biased gene expression, and consequently phenotypic changes in mammals.