Metabolic control of transcription: paradigms and lessons from Saccharomyces cerevisiae

Abstract

The comparatively simple eukaryote Saccharomyces cerevisiae is composed of some 6000 individual genes. Specific sets of these genes can be transcribed co-ordinately in response to particular metabolic signals. The resultant integrated response to nutrient challenge allows the organism to survive and flourish in a variety of environmental conditions while minimal energy is expended upon the production of unnecessary proteins. The Zn(II)2Cys6 family of transcriptional regulators is composed of some 46 members in S. cerevisiae and many of these have been implicated in mediating transcriptional responses to specific nutrients. Gal4p, the archetypical member of this family, is responsible for the expression of the GAL genes when galactose is utilized as a carbon source. The regulation of Gal4p activity has been studied for many years, but we are still uncovering both nuances and fundamental control mechanisms that impinge on its function. In the present review, we describe the latest developments in the regulation of GAL gene expression and compare the mechanisms employed here with the molecular control of other Zn(II)2Cys6 transcriptional regulators. This reveals a wide array of protein-protein, protein-DNA and protein-nutrient interactions that are employed by this family of regulators.

Mechanisms of Antisense Transcription Initiation from the 3′ End of the GAL10 Coding Sequence In Vivo

“…This is as expected since GAL7 is inactive in dextrose-containing growth medium. Further, sense RNA polymerase II does not associate with the GAL10 coding region in dextrose-containing growth medium because of Mig1p-mediated repression as well as the masking of the Gal4p activation domain by the repressor, Gal80p (60,61,(68)(69)(70)(71). Thus, the significantly high level of RNA polymerase II at the 3= end of the GAL10 coding sequence in dextrose-containing growth medium supports the association of RNA polymerase II with the antisense transcription initiation site.…”

“…Thus, similar to the oligo(dT) primer, the P1 primer can be used in cDNA synthesis to study the sense transcription of ACT1, ADH1, RPS5, and other genes (that are expressed in dextrose-and/or galactose-containing growth medium). Since sense transcription does not occur at the GAL gene cluster in dextrose-containing growth medium (60,61,(68)(69)(70)(71), the aforementioned RT-PCR analysis using a specific P1 primer would be useful in analyzing antisense transcripts from the GAL10 locus in dextrose-containing growth medium. Further, sense transcripts of ACT1 or ADH1 in dextrose-containing growth medium can be used as controls in the RT-PCR analysis of GAL10 antisense transcription.…”

“…2E, last lane). However, sense transcription of GAL10 and GAL7 was observed using the oligo(dT) primer in cDNA synthesis in galactose-containing growth medium as these GAL genes undergo sense transcription in galactose but not dextrose-containing growth medium (60,61,(68)(69)(70)(71). A long GAL10 antisense transcript may not be completely reverse transcribed by oligo(dT) or may not be efficiently polyadenylated, leading to the absence of PCR signal in the RT-PCR analysis using an oligo(dT) primer.…”

Regulation of Amino Acid, Nucleotide, and Phosphate Metabolism in Saccharomyces cerevisiae

“…Lys14 is a member of the Zn (II) 2 Cys 6 binuclear cluster family of transcriptional regulators, which are constitutively nuclear and found associated with promoter sequences of the genes they regulate (reviewed in Campbell et al 2008). As a consequence of a pathway intermediate controlling the capacity of Lys14 to activate gene expression, conditions that increase or decrease the flux through the pathway, positively or negatively, affect LYS gene expression.…”

Identification of a cis-acting factor modulating the transcription of FUM1, a key fumonisin-biosynthetic gene in the fungal maize pathogen Fusarium verticillioides

“…However, our observation also supports the hypothesis that orthologous TFs (most probably, but not necessarily, a narrow-domain TF located within the FUM cluster) may recognize these conserved cis-regulatory elements in the two species. Binding sites of TFs belonging to the Zinc binuclear cluster and possessing a Zn(II)2Cys6 motif, which are only found in fungi, share the CGG core contained in the motif identified in this study ( Campbell et al, 2008 andMacPherson et al, 2006). We therefore hypothesize that the TF binding to the putative cis-regulatory elements is a Zinc binuclear TF with a Zn(II)2Cys6 motif.…”