Interaction of Transcription Factors RFX1 and MIBP1 with the γ Motif of the Negative Regulatory Element of the Hepatitis B Virus Core Promoter

Abstract

The negative regulatory element (NRE) of the hepatitis B virus (HBV) core promoter contains three subregions which act synergistically to suppress core promoter activity. One of these subregions, NREγ, is active in both HeLa cervical carcinoma cells and Huh7 hepatoma cells and was found to be bound by a protein factor present in both cell types. Here we show that the transcription factor RFX1 can bind to NREγ and transactivate the core promoter through this site. Mutations which abrogated the gene-suppressive activity of NREγ prevented RFX1 from binding to NREγ. In addition, RFX1 can bind simultaneously, most likely as a heterodimer, with the transcription factor MIBP1 to NREγ. In the absence of a cloned MIBP1 gene for further studies, we hypothesize that RFX1 acts with MIBP1 to negatively regulate the core promoter activity through the NREγ site. The ability of RFX1 to transactivate the core promoter raises the possibility that RFX1 may play a dual role in regulating HBV gene expression.