Trans-homologous interactions identified in Hi-C data are associated with embryonic development

Interactions between chromosomes forming homologous pairs are known to be widespread in the fruit fly Drosophila melanogaster and present in other organisms. While these trans-homologous interactions affect regulation of gene expression, many details regarding their location, function and mechanisms of action are still unknown. The increased availability of phased Hi-C datasets made it possible to reliably infer such trans-homologous interactions. We have developed a tool called TransContactHiC to detect trans-homologous chromatin interactions in phased Hi-C data and we used it to re-analyze published in situ Hi-C data for heterozygotic Drosophila melanogaster cells: embryos and a fully differentiated cell line. We further assessed the frequency of cis- and trans-homologous interactions for equally sized genomic bins, and detected triads of genomic elements which exhibit significantly different frequency of trans-homologous interactions compared to the cis-homologous counterpart. We show that triads of genomic elements exhibiting significantly higher frequency of trans homologous interactions are characterized by their clustering within broader regulatory regions, proximity to DNase-seq peaks and presence of disrupted transcription factor motifs at the affected locus. We also show examples of annotated active cis-regulatory modules which might be affected by these differential trans-homologous interactions. Overall, our results show the functional relevance of the detected triads.