Multiple transcriptional activation complexes tether the yeast activator Met4 to DNA

The transcriptional regulation of the sulfur amino acid pathway in Saccharomyces cerevisiae depends on a single activator, Met4p, whose function requires different combinations of the auxiliary factors Cbf1p, Met28p, Met31p and Met32p. The first description of how these factors cooperate to activate transcription was provided by the identification of the Cbf1-Met4-Met28 complex which is assembled on the regulatory region of the MET16 gene. In this paper, we demonstrate that other pathways are used to recruit Met4p on the 5' upstream region of the two genes, MET3 and MET28. In these cases, Met4p is tethered to DNA through two alternative complexes associating Met4p with Met28p and either Met31p or Met32p. These complexes are formed over the AAACTGTG sequence, a cis-acting element found upstream of several MET genes. The identification of a domain within Met4p that mediates its interaction with Met31p and Met32p allowed in vivo analysis of the specificity of the Met4p-containing complexes. The results therefore demonstrate that the co-regulation of a single gene network may be gained through different molecular mechanisms. In addition the sulfur system exacerbates the structural variety of the nucleoprotein complexes in which a single bZIP factor can be engaged.