Using the same approach, several cellular transcription factors (CREB, ATF, YY1, STAT1, and STAT2) and chromatin modifying enzymes (PCAF, p300/CBP, HDAC1, SIRT1, and EZH2) have been shown to bind to the cccDNA in human hepatoma cells containing replicating HBV (Pollicino et al., 2006; Belloni et al., 2009, 2012). This evidence concerns the gene HDAC1 and hepatocellular carcinoma.