Transcriptional regulation by the ACE2 and SWI5 activators in yeast

Two independent transcriptional pathways regulated by the ACE2 and SWI5 genes have been identified in the yeast Saccharomyces cerevisiae. The CTSl and the HO pathways demonstrate remarkable similarity. Both genes are transcribed in the late Gl phase of the cell cycle. The HO gene encodes an endonuclease required for initiating the mating type switch, and the CTSl gene encodes chitinase required for degradation of the chitin septum that joins mother and daughter cells. Two homologous transcriptional activators regulate the HO and CTSl genes and demonstrate similarity as well. ACE2 and SWI5 encode transcriptional activators that contain Zn-finger DNA binding domains that are virtually identical. ACE2 and SWI5 show identical patterns of cell cycle regulated transcription and nuclear localization. ACE2 and SWI5 are transcribed during the G2 portion of the cell cycle. The translated Ace2 and Swi5 proteins remain cytoplasmic in G2 and then enter the nucleus as the cells complete mitosis. Furthermore, Ace2 and Swi5 bind to the same DNA sequences in vitro. Despite the functional similarities between the two pathways, they remain distinct. ACE2 does not regulate HO, and SWI5 does not regulate CTSl. Two mechanisms by which the two pathways remain distinct have been investigated. First, the specificity of activation by ACE2 at the CTSl promoter is due, in part, to negative regulation. Point mutations or deletions of a negative regulatory region within the CTSl promoter allow SW15 to function at CTSl, a gene that SW15 normally does not activate. It is proposed that a repressor binds to this region and prevents SW15 from activating CTSl. The second mechanism by which the pathways remain distinct is due, in part, to combinatorial control. The specificity of DNA binding by the Swi5 protein to the HO promoter is enhanced by an additional protein factor called GrflO. ACE2 fails to interact with GRFIO as demonstrated by both genetic and biochemical analysis. The inability of ACE2 to interact with GRFIO prevents ACE2 from functioning at the HO promoter.