RFX1 is identical to enhancer factor C and functions as a transactivator of the hepatitis B virus enhancer.

Abstract

Hepatitis B virus gene expression is to a large extent under the control of enhancer I (EnhI). The activity of EnhI is strictly dependent on the enhancer factor C (EF-C) site, an inverted repeat that is bound by a ubiquitous nuclear protein known as EF-C. Here we report the unexpected finding that EF-C is in fact identical to RFX1, a novel transcription factor previousiy cloned by virtue of its affinity for the HLA class II X-box promoter element. This finding has allowed us to provide direct evidence that RFX1 (EF-C) is crucial for EnhI function in HepG2 hepatoma cells; RFXl-specific antisense oligonucleotides appear to inhibit EnhI-driven expression of the hepatitis B virus major surface antigen gene, and in transfection assays, RFX1 behaves as a potent transactivator of EnhI. Interestingly, transactivation of EnhI by RFX1 (EF-C) is not observed in cell lines that are not of liver origin, suggesting that the ubiquitous RFX1 protein cooperates with liver-specific factors.

HBV integrants of hepatocellular carcinoma cell lines contain an active enhancer

“…A major protected area corresponds to the previously characterized EP element. The protected G-residues are identical to that reported for the in vitro DMS footprinting of the EP (EF-C) element (Ostapchuk et al, 1989), suggesting that the EP element in both cells bind at least the RFX1 protein (Blake et al, 1996;Katan et al, 1997;Siegrist et al, 1993). In PLC/PRF/5 cells, the analysed EP element has an additional contact point with the binding protein at the non-coding strand due to a T to C transition.…”

The Transcription Factor Regulatory Factor X1 Increases the Expression of Neuronal Glutamate Transporter Type 3

“…Thus, the X-box in the EAAT3 gene is a positively acting regulatory element for the expression of this gene. Positively acting regulatory elements of the X-box after binding to RFXs have been shown in most of the viral promoters and in the promoter of interleukin-5 receptor ␣ chain (18,20). However, negatively acting regulatory elements of the X-box after binding to RFXs have been shown in the promoters for genes, such as proliferating cell nuclear antigen and microtubule-associated protein 1A (17,19).…”

“…Mutations in the DNA binding domain of RFX5 cause bare lymphocyte syndrome or major histocompatibility complex antigen class II deficiency (8). RFX1, the prototypic mammalian RFX, has been shown to act as a potent transactivator of enhancer I for the hepatitis B virus major surface antigen gene in cells that are of liver origin (20). However, the physiological significance of RFX1-3 in the mammalian cells is not yet clear.…”

The kinase activity of c-Abl but not v-Abl is potentiated by direct interaction with RFXI, a protein that binds the enhancers of several viruses and cell-cycle regulated genes

“…The EP nucleo-protein complex contains at least two protein components, c-Abl and RFX1 (Dikstein et al, 1992;Siegrist et al, 1993). The EP associated c-Abl has a strong kinase activity (Dikstein et al, 1996).…”

“…RFX1, a 140 kDa protein, belongs to a family of DNA binding proteins conserved in evolution down to yeast (Reith et al, 1990(Reith et al, , 1994Steimle et al, 1995;Wu and McLeod, 1995;Emery et al, 1996). RFX1 binds the EP site and activates the HBV enhancer (Siegrist et al, 1993). However, when examined in isolation, not in the context of the enhancer, RFX1 was found to have multiple functional domains (Katan et al, 1997).…”