IFI16‐mediated repression of rcccDNA transcription is DDX5 and PRC2 dependent. (A) Immunofluorescence microscopy of Huh7 cells transfected for 72 h with prcccDNA and GFP‐Cre plasmids, without (−) and with (+) IFI16 encoding vector, and co‐transfected with 50 pM of indicated siRNAs. Quantification of HBc/Cre ratio from 1000 cells. Data are expressed as mean ± standard error of the mean (SEM) from n = 3. **p < 0.01, ***p < 0.001. (B) qRT‐PCR quantification of viral RNAs (total HBV RNA and preC/pgRNA) using RNA isolated from HepG2‐NTCP cells, transfected with indicated plasmids for 72 h. Data are expressed as mean ± SEM from three independent experiments. *p < 0.05, **p < 0.01, ***p < 0.001. (C) ChIP assays using IgG or indicated ChIP‐validated antibodies (FLAG, AcH3, and H3K27me3) and nuclear lysates from HepG2‐NTCP cells transfected for 72 h as in (A). Quantification of rcccDNA by PCR using P1 and P2 primers. Data are expressed as mean ± SEM from n = 3. **p < 0.01 ***p < 0.001, ns = not significant.