Seminar: Cis-regulatory effect of Human papillomavirus integration in cervical cancers

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2023-11-22: by Sabarinathan Radhakrishnan, National Centre for Biological Sciences (NCBS-TIFR), Bengaluru. The seminar will take place 14:30-15:30 at University of Copenhagen, Frederiksberg Campus, Stalden, bygning 1-09, Ridebanevej 6, 1. sal, 1870 Frederiksberg C.

Human papillomavirus (HPV) DNA integration is often found in the nuclear genome of cervical tumours, however, its effect on host chromatin structure and gene regulation remain largely unknown. In this talk, I will share some of our recent findings from a systematic analysis of the genome-wide patterns of HPV integrations and associated gene expression changes (from patient samples) in the context of chromatin states and topologically associating domains (TADs) from cell lines. We found that the HPV integrations are significantly enriched in active and depleted in inactive chromatin regions. Nevertheless, the flanking host regions of HPV integration regions showed upregulation of transcriptional activity, regardless of the host chromatin state. Interestingly, the upregulation (both local and long-range) is mostly constrained within HPV-integrated TADs and not affecting the adjacent TADs. A subset of TADs showed recurrent HPV integrations (across patients) associated with overexpression of oncogenes (such as MYC, PVT1, TP63 and ERBB2) within them regardless of the proximity to the integration sites. Finally, by using HiC and 4C analyses, we demonstrate the long-range effect of HPV integration on MYC/PVT1 expression in the HeLa cell line. Together, these results suggest the cis-regulatory potential of HPV integration through local changes in the chromatin interactions and gene expression.

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