Integrating Hi-C data and RNA-seq data to reveal the 3D genome in sheep

The chromatin structure of eukaryotic cell has an important role in gene regulation. However, the chromatin structure of different tissues in relation to gene expression have been less reported, especially in animal genome model such as sheep. Here, we aimed to explore the relationship between three-dimensional (3D) chromatin structure and gene regulation through in High throughput chromosome conformation capture (Hi-C) and RNA-sequencing (RNA-seq) of hypothalamus, liver, muscle, and tail fat in sheep. A high-resolution 3D chromatin interaction map was generated to examine different 3D genome hierarchies including A/B compartments (A being transcriptionally active and gene-rich, B being transcriptionally inactive and gene-poor), topologically associated domains (TADs), and chromatin loops by Hi-C. Gene expression analysis revealed significant differences between A and B compartments, with B compartments also harboring highly expressed genes. Gene expression differed significantly between TAD boundaries and the internal regions of TADs, with TAD boundaries frequently aligning with compartment boundaries. This suggests that compartmentalization plays a facilitating role in the formation of TADs in sheep. Liver and muscle tissues showed significantly more cis-significant interaction sites, related to the complex functional and metabolic needs of tissues. Finally, we calculated the proportions of shared and unique regions across A compartments, TAD boundaries, and chromatin loops. Completely shared and unique patterns were found to be rare, with most regions being partially shared. This study offers a large dataset of chromosomes that can aid future investigations into genetic and tissue-specific diseases in sheep.