Molecular mechanism of the multiple regulation of the Saccharomyces cerevisiae ATF1 gene encoding alcohol acetyltransferase

The ATF1 gene encodes an alcohol acetyl transferase (AATase), that catalyse s the synthesis of acetate esters from acetyl CoA and several kinds of alco hols. ATF1 transcription is negatively regulated by unsaturated fatty acids and oxygen. A series of analyses of the ATF1 promoter identified an 18 bp element essential for transcriptional activation. Ligation of the 18 bp ele ment into a plasmid carrying the CYC1 promoter deleted UAS-activated transc ription and conferred transcriptional repression by unsaturated fatty acids . The 18 bp element contains a binding sequence for Rap1p, which is a trans criptional repressor and activator. In vitro binding studies showed that Ra p1p binds to the 18 bp element essential for transcriptional activation. Th e results of internal deletion studies of the promoter region suggested tha t there was also a region responsible for ATF1 oxygen regulation. This regi on contained the consensus binding sequence for the hypoxic repressor Rox1p . In vitro binding studies showed that Rox1p binds to the region responsibl e for oxygen regulation. To investigate the effect of the hypoxic repressor complex on transcription, ATF1 expression was measured in rox1, tup1 and s sn6 disruptant strains. It was found that rox1, tup1 and ssn6 disruption ca used elevated expression of ATF1 under aerobic conditions. Thus, the activa tion of ATF1 transcription is dependent on Rap1p, and the Rox1p-Tup1p-Ssn6p hypoxic repressor complex is responsible for repression by oxygen. Further more, a study of ATF1 expression in a sch9 null mutant suggested that the S ch9p protein kinase is involved in ATF1 transcriptional activation. Copyrig ht (C) 1999 John Wiley & Sons, Ltd.