Joint modeling of histone modifications in 3D genome shape through Hi-C interaction graph

Abstract

Chromosome conformation capture experiments such as Hi-C are used to map the three-dimensional spatial organization of genomes. Even though Hi-C interactions are not biased towards any of the histone modifications, previous analysis has revealed denser interactions around many histone modifications. Nevertheless, simultaneous effects of these modifications in Hi-C interaction graph have not been fully characterized yet, limiting our understanding of genome shape. Here, we propose Coverage Hi-C to decompose Hi-C interaction graph in terms of known histone modifications. Coverage Hi-C is based on set multicover with pairs, where each Hi-C interaction is covered by histone modification pairs. We find 4 histone modifications H3K4me1, H3K4me3, H3K9me3, H3K27ac to be significantly predictive of most Hi-C interactions across species and cell types. Coverage Hi-C is quite effective in predicting Hi-C interactions and topologically-associated domains (TADs) in one species, given it is trained on another species or cell types.