biostudies-literatureWarburton AIntramural NIH HHSDivision of Intramural Research, National Institute of Allergy and Infectious Diseasese1013454https://www.ebi.ac.uk/biostudies/studies/S-EPMC12440168biostudies-literatureUnknown21(9)Human papillomaviruses (HPVs) maintain their genomes as minichromosomes in the nuclei of infected keratinocytes. This study investigates the association of HPV31 genomes with host chromatin using both HiC and 4C-seq chromosome conformation capture techniques. We show that HPV31 genomes preferentially associate with transcriptionally active A compartments of host chromatin, regions of open chromatin defined by ATAC-seq, and super-enhancers defined by Brd4 and H3K27ac ChIP-seq. The viral genome association sites were also highly correlated with genomic loci previously identified as common HPV integration sites in cervical cancers. Recent studies have shown that transcriptionally active sites are prone to dsDNA breaks, and we find a strong correlation among dsBREAK datasets with transcriptionPLoS pathogensHuman papillomavirus genomes associate with active host chromatin during persistent viral infection.PMC12440168ZIA AI000713ZIA AI001223Z01 AI000713McBride AAMarkowitz TEMajumder KWarburton AMiranda JLfalseHuman papillomavirus genomes associate with active host chromatin during persistent viral infection.Human papillomaviruses (HPVs) maintain their genomes as minichromosomes in the nuclei of infected keratinocytes. This study investigates the association of HPV31 genomes with host chromatin using both HiC and 4C-seq chromosome conformation capture techniques. We show that HPV31 genomes preferentially associate with transcriptionally active A compartments of host chromatin, regions of open chromatin defined by ATAC-seq, and super-enhancers defined by Brd4 and H3K27ac ChIP-seq. The viral genome association sites were also highly correlated with genomic loci previously identified as common HPV integration sites in cervical cancers. Recent studies have shown that transcriptionally active sites are prone to dsDNA breaks, and we find a strong correlation among dsBREAK datasets with transcription2025-01-01T00:00:00Z2025 Sep2026-06-01T06:20:59.016Z2026-04-08T09:44:29.441ZS-EPMC124401684089286910.1371/journal.ppat.1013454