FIGURE 1.

Schematic representation of the chromatin changes on cccDNA in relation to viral replication. The acetylation status of cccDNA-bound histones and the recruitment of chromatin modifying enzymes onto cccDNA change in response to IFNα treatment and HBx status. In high viral replication of the wild type virus or in the absence of IFNα treatment, cccDNA-bound histones are hyperacetylated, cccDNA-associated chromatin is in an open configuration and pgRNA is actively transcribed. In cells replicating an HBx mutant and in IFNα-treated cells, cccDNA-bound histones are hypoacetylated, the recruitment of the p300 acetyltransferase is severely impaired, whereas the recruitment of the histone deacetylases (HDACs) hSirt1 and HDAC1 as well as the polycomb protein enhancer of zeste homolog 2 (Ezh2) is increased. In the absence of HBx, hypoacetylation is accompanied by the recruitment of heterochromatin protein 1 factors (HP1) and SET domain, bifurcated 1(SETDB1). Modified from Belloni et al. (2009).