title: Histone H3 Ser10 phosphorylation-independent function of Snf1 and Reg1 proteins rescues a gcn5- mutant in HIS3 expression.
abstract: Gcn5 protein is a prototypical histone acetyltransferase that controls transcription of multiple yeast genes. To identify molecular functions that act downstream of or in parallel with Gcn5 protein, we screened for suppressors that rescue the transcriptional defects of HIS3 caused by a catalytically inactive mutant Gcn5, the E173H mutant. One bypass of Gcn5 requirement gene (BGR) suppressor was mapped to the REG1 locus that encodes a semidominant mutant truncated after amino acid 740. Reg1(1-740) protein does not rescue the complete knockout of GCN5, nor does it suppress other gcn5- defects, including the inability to utilize nonglucose carbon sources. Reg1(1-740) enhances HIS3 transcription while HIS3 promoter remains hypoacetylated, indicating that a noncatalytic function of Gcn5 is targeted by this suppressor protein. Reg1 protein is a major regulator of Snf1 kinase that phosphorylates Ser10 of histone H3. However, whereas Snf1 protein is important for HIS3 expression, replacing Ser10 of H3 with alanine or glutamate neither attenuates nor augments the BGR phenotypes. Overproduction of Snf1 protein also preferentially rescues the E173H allele. Biochemically, both Snf1 and Reg1(1-740) proteins copurify with Gcn5 protein. Snf1 can phosphorylate recombinant Gcn5 in vitro. Together, these data suggest that Reg1 and Snf1 proteins function in an H3 phosphorylation-independent pathway that also involves a noncatalytic role played by Gcn5 protein.
authors.affiliation: 401 BCH Building, Department of Biochemistry and Molecular Biology, Michigan State University, East Lansing, MI 48824. kuom@msu.edu.
authors.forename: Yang
authors.initials: Y
authors.lastname: Liu
authors.forename: Xinjing
authors.initials: X
authors.lastname: Xu
authors.forename: Soumya
authors.initials: S
authors.lastname: Singh-Rodriguez
authors.forename: Yan
authors.initials: Y
authors.lastname: Zhao
authors.forename: Min-Hao
authors.initials: MH
authors.lastname: Kuo
mesh_terms: D000483:Alleles; D000595:Amino Acid Sequence; D001483:Base Sequence; D015966:Gene Expression Regulation, Fungal; D018698:Glutamic Acid / Q000235:genetics / Q000378:metabolism; D051548:Histone Acetyltransferases / Q000172:deficiency* / Q000235:genetics / Q000378:metabolism*; D006657:Histones / Q000737:chemistry / Q000378:metabolism*; D006836:Hydro-Lyases / Q000235:genetics* / Q000378:metabolism; D008969:Molecular Sequence Data; D009154:Mutation / Q000235:genetics; D010641:Phenotype; D010749:Phosphoprotein Phosphatases / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D010768:Phosphoserine / Q000378:metabolism*; D011485:Protein Binding; D054645:Protein Phosphatase 1; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism*; D012441:Saccharomyces cerevisiae / Q000235:genetics / Q000378:metabolism; D029701:Saccharomyces cerevisiae Proteins / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D013489:Suppression, Genetic / Q000235:genetics; D000099224:p300-CBP-Associated Factor
chemical_list: D018698:Glutamic Acid; D051548:Histone Acetyltransferases; D006657:Histones; D006836:Hydro-Lyases; D010749:Phosphoprotein Phosphatases; D010768:Phosphoserine; D054645:Protein Phosphatase 1; D017346:Protein Serine-Threonine Kinases; D029701:Saccharomyces cerevisiae Proteins; C501392:GCN5 protein, S cerevisiae; D000099224:p300-CBP-Associated Factor; C071570:SNF1-related protein kinases; C070829:REG1 protein, S cerevisiae; C021434:imidazoleglycerolphosphate dehydratase