Abstract
Basic helix-loop-helix domains in yeast regulatory proteins Ino2 and Ino4 mediate formation of a heterodimer which binds to and activates expression of phospholipid biosynthetic genes. The human proto-oncoprotein c-Myc (Myc) and its binding partner Max activate genes important for cellular proliferation and contain functional domains structure and position of which strongly resembles Ino2 and Ino4. Since Ino2-Myc and Ino4-Max may be considered as orthologs we performed functional comparisons in yeast. We demonstrate that Myc and Max could be stably synthesized in S. cerevisiae and together significantly activated a target gene of Ino2/Ino4 but nevertheless were unable to functionally complement an ino2 ino4 double mutant. We also map two efficient transcriptional activation domains in the N-terminus of Myc (TAD1: aa 1-41 and TAD2: aa 91-140), corresponding to TAD positions in Ino2. We finally show that coactivators such as TFIID subunits Taf1, Taf4, Taf6, Taf10 and Taf12 as well as ATPase subunits of chromatin remodelling complexes Swi2, Sth1 and Ino80 previously shown to interact with TADs of Ino2 were also able to bind TADs of Myc, supporting the view that heterodimers Ino2/Ino4 and Myc/Max are evolutionary related but have undergone transcriptional rewiring of target genes.