Hi-C interaction graph analysis reveals the impact of histone modifications in chromatin shape

Chromosome conformation capture experiments such as Hi-C map the three-dimensional spatial organization of genomes in a genome-wide scale. 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 ChromatinCoverage and its extension TemporalPrizeCoverage methods to decompose Hi-C interaction graph in terms of known histone modifications. Both methods are based on set multicover with pairs, where each Hi-C interaction is tried to be 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, cell types and cell cycles. The proposed methods are quite effective in predicting Hi-C interactions and topologically-associated domains in one species, given it is trained on another species or cell types. Overall, our findings reveal the impact of subset of histone modifications in chromatin shape via Hi-C interaction graph.