THE BIFUNCTIONAL PROTEIN DCOH MODULATES INTERACTIONS OF THE HOMEODOMAIN TRANSCRIPTION FACTOR HNF1 WITH NUCLEIC-ACIDS

The hepatocyte nuclear factor-1 (HNF1) is a homeodomain transcription factor that binds DNA as a dimer. HNF1 dimers associate with two molec ules of DCoH, a bifunctional protein that also has an enzymatic functi on in the tetrahydrobiopterin regeneration, to form stable heterotetra mers also capable DNA binding. Employing purified, recombinant HNF1, H NF1/DCoH heterotetramers and DCoH homotetramers we investigated whethe r DCoH affects interactions of HNF1 with nucleic acids. Although we de tected no direct binding DCoH to DNA or RNA, DCoH stabilized HNF1/DNA complexes and promoted interactions with sup-optimal DNA target sequen ces such as the human alpha 1-antitrypsin TATA box region. Importantly , we also observed interactions of HNF1 with RNA, but these interactio ns were completely abolished when HNF1 was complexed with DCoH. Intere stingly, DCoH retains its enzymatic activity while complexed with HNF1 . Our results document intermolecular regulation of HNF1 binding to nu cleic acids by DCoH. (C) 1997 Academic Press Limited