Snf1p regulates Gcn5p transcriptional activity by antagonizing Spt3p.
The budding yeast Gcn5p is a prototypic histone acetyltransferase controlling transcription of diverse genes. Here we show that Gcn5p is itself regulated by Snf1p and Spt3p. Snf1p likely controls Gcn5p via direct interaction. Mutating four residues in the Gcn5p catalytic domain, T203, S204, T211, and Y212 (TSTY), phenocopies snf1 null cells, including Gcn5p hypophosphorylation, hypoacetylation at the HIS3 promoter, and transcriptional defects of the HIS3 gene. However, overexpressing Snf1p suppresses the above phenotypes associated with the phosphodeficient TSTY mutant, suggesting that it is the interaction with Snf1p important for Gcn5p to activate HIS3. A likely mechanism by which Snf1p potentiates Gcn5p function is to antagonize Spt3p, because the HIS3 expression defects caused by snf1 knockout, or by the TSTY gcn5 mutations, can be suppressed by deleting SPT3. In vitro, Spt3p binds Gcn5p, but the interaction is drastically enhanced by the TSTY mutations, indicating that a stabilized Spt3p-Gcn5p interaction may be an underlying cause for the aforementioned HIS3 transcriptional defects. These results suggest that Gcn5p is a target regulated by the competing actions of Snf1p and Spt3p.
Liu
Yang
Y
Program in Genetics, Michigan State University, East Lansing, Michigan 48824, USA.
Xu
Xinjing
X
Kuo
Min-Hao
MH
D000107:Acetylation; D000409:Alanine; D019943:Amino Acid Substitution; D001483:Base Sequence; D020134:Catalytic Domain; D017353:Gene Deletion; D015966:Gene Expression Regulation, Fungal; D055786:Gene Knockout Techniques; D051548:Histone Acetyltransferases / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D006657:Histones / Q000378:metabolism; D009154:Mutation; D010750:Phosphoproteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D010766:Phosphorylation; D017346:Protein Serine-Threonine Kinases / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D012441:Saccharomyces cerevisiae / Q000235:genetics* / Q000378:metabolism*; D029701:Saccharomyces cerevisiae Proteins / Q000037:antagonists & inhibitors* / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D014157:Transcription Factors / Q000037:antagonists & inhibitors* / Q000172:deficiency / Q000235:genetics / Q000378:metabolism; D014158:Transcription, Genetic; D015533:Transcriptional Activation; D000099224:p300-CBP-Associated Factor
D000409:Alanine; D051548:Histone Acetyltransferases; D006657:Histones; D010750:Phosphoproteins; D017346:Protein Serine-Threonine Kinases; D029701:Saccharomyces cerevisiae Proteins; D014157:Transcription Factors; C075582:SPT3 protein, S cerevisiae; C501392:GCN5 protein, S cerevisiae; D000099224:p300-CBP-Associated Factor; C071570:SNF1-related protein kinases