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bioRxiv · 10.1101/2025.04.25.648339

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

Machnicka, M. A.·Jankowski, A.
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Abstract

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.

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Machnicka, M. A., Jankowski, A.. 2025-04-26. Trans-homologous interactions identified in Hi-C data are associated with embryonic development. https://doi.org/10.1101/2025.04.25.648339

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