THE RESTRICTED PROMOTER ACTIVITY OF THE LIVER TRANSCRIPTION FACTOR HEPATOCYTE NUCLEAR FACTOR-3-BETA INVOLVES A CELL-SPECIFIC FACTOR AND POSITIVE AUTOACTIVATION

The transcription factor hepatocyte nuclear factor 3 (HNF-3) is involved in the coordinate expression of several liver genes. HNF-3 DNA binding activity is composed of three different liver proteins which recognize the same DNA site. The HNF-3 proteins (designated-alpha, beta, and gamma) possess homology in the DNA binding domain and in several additional regions. To understand the cell-type-specific expression of HNF-3-beta, we have defined the regulatory sequences that elicit hepatoma-specific expression. Promoter activity requires - 134 bp of HNF-3-beta proximal sequences and binds four nuclear proteins, including two ubiquitous factors. One of these promoter sites interacts with a novel cell-specific factor, LF-H3-beta, whose binding activity correlates with the HNF-3-beta tissue expression pattern. Furthermore, there is a binding site for the HNF-3 protein within its own promoter, suggesting that an autoactivation mechanism is involved in the establishment of HNF-3-beta expression. We propose that both the LF-H3-beta and HNF-3 sites play an important role in the cell-type-specific expression of the HNF-3-beta transcription factor.