THE DNA-BINDING ACTIVITY AND THE DIMERIZATION ABILITY OF THE THYROID TRANSCRIPTION FACTOR-I ARE REDOX REGULATED

The DNA binding activity of the thyroid transcription factor-1 (TTF-1) , a homeodomain-containing protein implicated in the control of thyroi d- and lung-specific transcription, is controlled, in vitro, by the re dox potential, Oxidation decreases TTF-1 DNA binding activity, which i s fully restored upon exposure to reducing agents. The decrease in DNA binding activity is due to the formation of disulfide bond(s), formed between two specific cysteine residues located outside the TTF-1 home odomain; hence, oxidation does not appear to directly hinder TTF-1/DNA contacts, Disulfide bond formation seems to stabilize preexisting, lo osely associated, TTF-1 dimers, which, upon oxidation, proceed in the formation of specific, higher order oligomers.