IFN-λ1 decreases miR-122 transcription through down regulation of HNF4α.

<p><b>(A and B)</b> S3-GFP and R4-GFP cells were treated either IFN-α (1000 I.U/mL) or IFN-λ (100ng/mL). Cells were harvested at 1, 4 and 24 hours and then HNF4α mRNA levels were measured by real-time RT-PCR. <b>(C)</b> Protein levels of HNF4-α measured by Western blot in R4-GFP and S3-GFP after 4 hours of treatment with either 1000 IU/mL of IFN-α or 100ng/mL of IFN-λ. <b>(D)</b> Equal amount of cell lysates from R4-GFP cells were incubated with biotinylated double-stranded oligonucleotides corresponding to the two DR1 motifs in miR-122 promoter and with sterptavidin-agarose beads. The precipitated complexes were subjected to SDS-PAGE and Western blotting for HNF4α and PPAR-γ. <b>(E)</b> Quantification of the bands in Fig 5D <b>(F)</b> Schematic representation of putative HNF4α binding sites in human miR-122 gene promoters and the mechanisms for how IFN-λ1 decreases miR-122 transcription through reduced binding of HNF4α to DR1 element, **p≤0.01, ***p≤0.001.