Fig. 6

Modulation of iron metabolism-related genes after HBV infection. a) Venn diagram showing the intersection between the 643 RNA-seq (DEGs) and ATAC-seq (DAGs) comodulated genes and iron metabolism genes (524 genes from 23 iron-related MSigDB gene sets; see the Supplementary Information and Table S10). b) Heatmap of RNA-seq median Transcripts Per Million (TPM) values, stratified by organ, in the GTEx project database for the 39-iron metabolism-related genes comodulated in RNA-seq (DEGs) and ATAC-seq (DAGs) after HBV infection (liver iron signature). The hierarchal clustering analysis indicate a clear separation between liver (red rectangle) and other tissues. c) Expression of the 6 genes involved in iron uptake (CP, TF, TFR2 and TFRC) and iron homeostasis (NCOA4, SLC11 A2) present in the liver iron signature in a RNA-seq dataset of HBV infected hepatocytes [10]. Results are expressed as Log2 Fold Changes (Log2 FC) in HBV vs MOCK conditions at the indicated times p.i. CP, TF, TFR2, TFRC, NCOA4, SLC11 A2. d) Quantitative Real-Time PCR analysis of 3 iron-uptake/homeostasis genes in the liver iron signature (TF, TFRC and SLC11 A2) in MOCK and HBV-infected PHHs from seven independent experiments. Data are expressed as the 2-\(\Delta\)CT of target genes normalized over the GUSb housekeeping gene. Whiskers represent the minimum and maximum values. p-values were calculated using the Wilcoxon matched-pairs signed rank test