Fig. 3: Human and viral genomes on hybrid ecDNA interacted directly with each other. | Nature Communications

Fig. 3: Human and viral genomes on hybrid ecDNA interacted directly with each other.

From: Inhibition of human-HPV hybrid ecDNA enhancers reduces oncogene expression and tumor growth in oropharyngeal cancer

Fig. 3: Human and viral genomes on hybrid ecDNA interacted directly with each other.

Cis-interactions between enhancer and HPV in hybrid ecDNA were analyzed by HiC-seq. Human genome regions on hybrid ecDNA were divided into 2 segments (S1 and S2). The S1 enhancer region interacted with the HPV L1 region (black arrow in A and B), and the S2 enhancer region significantly interacted with the HPV E6/E7 regions in HMS001 (Right green arrow in A and B). Blue dots indicate significant interactions. On the other hand, there was no such interaction in SCC154 that lacked hybrid ecDNA (C). This phenomenon was confirmed in PDX tumors (D–F). In PDX_A, the enhancer existed only in the S1 segment, and the S1 enhancer region significantly interacted with the HPV L1 and E6/E7 regions in PDX_A (black and yellow arrows in D and E). Blue dots indicate significant interactions. On the other hand, there was no such interaction in PDX_C that lacked hybrid ecDNA (F). Although each hybrid ecDNA structure was unique, each of the human enhancer regions closely interacted with HPV, confirming the direct interaction of the human and viral genomes on the hybrid ecDNAs.

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