Effect of HBV on the methylation profile of CpGs and competition with the GR for binding to the consensus GRE in the MAT1A promoter.
A, putative GRE-binding sites in the 5′-flanking region of the MAT1A gene are underlined. The human MAT1A-GRE1 and MAT1A-GRE2 were compared with the consensus GRE and the palindromic GRE. B, color of the circles is related to the percent of methylation in each CpG site. C, effect of HBV on the methylation profile of the CpG sites for the MAT1A promoter sequence. D, effect of HBV on the relative luciferase activity of the MAT1A promoter when four CpG sites were mutated in a wild-type pMAT1A-1.4Luc plasmid. *, p < 0.05. E, GR-binding profiles were examined by ChIP assays in HepG2.2.15 cells. Productions of Chip-GRE1, Chip-GRE2, and Chip-HBV were quantified by qPCR. *, p < 0.05. F, analyses of the effect of Dex on the binding of the GR to GRE of HBV (P3), and GRE1 (P1) and GRE2 (P2) of the MAT1A promoter by EMSA. Shown is a representative result from three independent experiments. N.E., nuclear extraction.