Fig. 3

Correlative analyses of HBV cccDNA-hepatocyte genome association and several chromatin structure markers on chromosome 1 in HepaRG, HepG2.2.15 and HepG2 H1.3 cells. a We performed correlation analyses between sites of HBV cccDNA enrichment with respect to transcribed regions. To assess the resolution of putative correlations, we applied different bin sizes for analyses. The graphs quintessentially illustrate chromosome 1 in three different cell lines (HepaRG, HepG2.2.15, HepG2H1.3) and chromosomes 18 and 19 in HepaRG cells. Importantly, R² indicates best correlation when larger resolution windows of 50 kb or 250 kb were selected. b At the top a human chromosome 1 ideogram is outlined as a reference, including GC content and DNase I hypersensitivity (both taken from the UCSC genome browser). DNase I hypersensitivity peaks are presented in grayscale and signals in blue scale. Below, genome-wide data from 4C and ChIP-seq mapping of HBx and cccDNA are presented for chromosome 1 in three different human hepatocyte cell lines (HepaRG, HepG2.2.15 and HepG2 H1.3 cells), each in a separate box. For each cell line (from top to bottom) this figure shows 4C-derived cccDNA enrichment, HBx enrichment (displayed as a negative signal for the sake of readability), the degree of correlation of cccDNA and genomic mRNA transcription and cccDNA transcription (displayed as a negative signal for the sake of readability). For HepaRG the gene transcription track is an overlay of 4 different time points from day 0 of infection to day 12 post-infection. Below indicated are CHIP-seq derived enrichments of cccDNA, HBx, Pol2, H3K36me3 and H3K4me3. The color-coding reference of the degrees of correlation and coverage are indicated in the legend at the bottom of the figure. This figure reveals correlative mapping using a 50 kb bin size for analyses of HBx and cccDNA with respect to the GC content track and DNase I hypersensitivity (top), gene transcription, Pol2, H3K36me3 and H3K4me3 (see also: https://genome.ucsc.edu/cgi-bin/hgTracks?hgS_doOtherUser=submit&hgS_otherUserName=janzop&hgS_otherUserSessionName=hsa_all_cccDNA_HBx_mRNA). Further examples of human chromosomes 18 (gene poor) and 19 (gene rich) are shown in Additional file 1: Figure S5