High impact information on RGT1

• It is required for glucose-stimulated regulation of Rgt1, a repressor of several glucose-induced HXT genes [1].
• Rgt1 binds in vivo to multiple sites in the HXT3 promoter in a nonadditive, synergistic manner, leading to synergistic repression of HXT3 transcription [2].
• These results suggest that glucose regulates the DNA-binding ability of Rgt1 by inducing its phosphorylation [2].
• We show that glucose inhibits the DNA-binding ability of Rgt1, thereby relieving repression of HXT gene expression [2].
• We identified the Rgt1 consensus binding site sequence 5'-CGGANNA-3', multiple copies of which are present in all HXT promoters regulated by Rgt1 [2].

Biological context of RGT1

• The presence of tandem repeats of the putative Rgt1p binding site gave results similar to those of the DDSE, suggesting that loss of repression is due to the presence of Rgt1p footprint in the multicopy DDSE [3].
• Thus, two different glucose signal transduction pathways converge on Rgt1 to regulate expression of glucose transporters [4].
• Rgt1 is phosphorylated in vitro by all three isoforms of PKA, and this requires several serine residues located in PKA consensus sequences within Rgt1 [4].
• Another region of Rgt1 (320-380) is required for normal transcriptional activation, and sequences flanking this region (310-320 and 400-410) regulate this function [5].

Anatomical context of RGT1

• In contrast, delivery of Rgt1 to fibroblasts did not modify HXT1-MIN responsiveness [6].

Associations of RGT1 with chemical compounds

• The RGT1 gene of Saccharomyces cerevisiae plays a central role in the glucose-induced expression of hexose transporter (HXT) genes [7].
• PKA and the consensus serine residues of Rgt1 are required for glucose-induced removal of Rgt1 from the HXT promoters and for induction of HXT expression [4].

Physical interactions of RGT1

• Expression was elevated to a high level in an rgt1 mutant in the absence of Snf3p suggesting that this DDSE region contains binding sites for the Rgt1p transcriptional repressor/activator [3].
• We report that Rgt1 interacts with Std1 and Mth1 in a yeast two-hybrid assay and co-immunoprecipitates with both proteins in vivo only when glucose is absent [8].
• Additional gel shift assays narrowed the Rgt1 binding site to the SUC2-B element within the SUC2 UAS, which is similar to previously identified Rgt1 binding sites present in other genes [9].

Regulatory relationships of RGT1

• Rgt1 represses HXK2 expression by binding specifically to the motif (CGGAAAA) located at -395 bp relative to the ATG translation start codon in the HXK2 promoter [10].
• It is likely that Rgt1 stimulates the expression of an activator of the HXT1 gene at high concentrations of glucose [11].
• In vivo levels of invertase activity in an rgt1Delta strain were reduced relative to an isogenic RGT+ strain when these strains were grown under inducing (low glucose) conditions, suggesting that Rgt1 may have a role in the activated transcription of SUC2 [9].

Other interactions of RGT1

• HXT1 expression is also induced by high glucose levels through another regulatory mechanism: rgt1 mutants still require high levels of glucose for maximal induction of HXT1 expression [12].
• Disappearance of Std1 in response to glucose is accelerated when glucose induction of STD1 expression due to feedback regulation by Rgt1 is prevented [13].
• Disruption of the RGT1 gene causes an 18-fold increase in the level of HXK2 transcript in the absence of glucose [10].
• The glucose transporter Snf3p, which appears to be a low-glucose sensor, is required for inhibition of Rgt1p repressor function by low levels of glucose [7].
• Rgt2p, a glucose transporter that functions as a high-glucose sensor, is required for conversion of Rgt1p into an activator by high levels of glucose [7].

Analytical, diagnostic and therapeutic context of RGT1

• Here we provide evidence that the multicopy DDSE suppression is due to the titration of the Rgt1p transcriptional repressor [3].
• Candidate target genes were verified by testing for Rgt1 binding to their promoters by chromatin immunoprecipitation and by measuring the regulation of the expression of promoter lacZ fusions [14].

References