Coordinated regulation and inositol-mediated and fatty acid-mediated repression of fatty acid synthase genes in Saccharomyces cerevisiae.

Abstract

In Saccharomyces cerevisiae, FAS1, FAS2, and FAS3 are the genes involved in saturated fatty acid biosynthesis. The enzymatic activities of both fatty acid synthase (FAS) and acetyl-CoA carboxylase are reduced 2- to 3-fold when yeast cells are grown in the presence of exogenous fatty acids. The mRNA levels of the FAS genes are correspondingly lower under repressive conditions. Expression of the FAS-lacZ reporter gene is also regulated by fatty acids. When a FAS2 multicopy plasmid is present in the cells, expression of both FAS1 and FAS3 increases. Thus, the FAS genes are coordinately regulated. Deletion analyses of the regulatory regions of FAS1 and FAS2 revealed common regulatory sequences. These include the GGCCAAAAAC and AGCCAAGCA sequences that have a common GCCAA core sequence and the UASINO (upstream activation sequence). Derepression of the FAS genes in the absence of exogenous inositol is not observed when UASINO is mutated, indicating that this cis element is a positive regulator of these genes. The GCCAA elements and UASINO act synergistically for optimal expression of the FAS genes.