title: Gcn4p-mediated transcriptional repression of ribosomal protein genes under amino-acid starvation.
abstract: Gcn4p is a well-characterized bZIP transcription factor that activates more than 500 genes encoding amino acids and purine biosynthesis enzymes, and many stress-response genes under various stress conditions. Under these stresses, it had been shown that transcriptions of ribosomal protein (RP) genes were decreased. However, the detailed mechanism of this downregulation has not been elucidated. In this study, we present a novel mechanistic model for a repressive role of Gcn4p on RP transcription, especially under amino-acid starvation. It was found that Gcn4p bound directly to Rap1p, which in turn inhibited Esa1p-Rap1p binding. The inhibition of Esa1p recruitment to RP promoters ultimately reduced the level of histone H4 acetylation and RP transcription. These data revealed that Gcn4p has simultaneous dual roles as a repressor for RP genes as well as an activator for amino-acid biosynthesis genes. Moreover, our results showed evidence of a novel link between general control of amino-acid biosynthesis and ribosome biogenesis mediated by Gcn4p at an early stage of adaptation to amino-acid starvation.
authors.affiliation: Laboratory of Biochemistry, School of Life Sciences and Biotechnology, Korea University, Seoul, Republic of Korea.
authors.forename: Yoo Jin
authors.initials: YJ
authors.lastname: Joo
authors.forename: Jin-Ha
authors.initials: JH
authors.lastname: Kim
authors.forename: Un-Beom
authors.initials: UB
authors.lastname: Kang
authors.forename: Myeong-Hee
authors.initials: MH
authors.lastname: Yu
authors.forename: Joon
authors.initials: J
authors.lastname: Kim
mesh_terms: D000596:Amino Acids / Q000172:deficiency*; D050976:Basic-Leucine Zipper Transcription Factors / Q000235:genetics / Q000378:metabolism*; D015152:Blotting, Northern; D015153:Blotting, Western; D015966:Gene Expression Regulation, Fungal; D051548:Histone Acetyltransferases / Q000235:genetics / Q000378:metabolism; D047468:Immunoprecipitation; D011401:Promoter Regions, Genetic; D012333:RNA, Messenger / Q000235:genetics; D012097:Repressor Proteins / Q000235:genetics / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012269:Ribosomal Proteins / Q000235:genetics* / Q000378:metabolism; D012441:Saccharomyces cerevisiae / Q000235:genetics / Q000254:growth & development / Q000378:metabolism*; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics / Q000378:metabolism*; D000089804:Shelterin Complex; D034501:Telomere-Binding Proteins / Q000235:genetics / Q000378:metabolism; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism; D014158:Transcription, Genetic
chemical_list: D000596:Amino Acids; D050976:Basic-Leucine Zipper Transcription Factors; C501391:GCN4 protein, S cerevisiae; C440829:RAP1 protein, S cerevisiae; D012333:RNA, Messenger; D012097:Repressor Proteins; D012269:Ribosomal Proteins; D029701:Saccharomyces cerevisiae Proteins; D000089804:Shelterin Complex; D034501:Telomere-Binding Proteins; D014157:Transcription Factors; C496551:Esa1 protein, S cerevisiae; D051548:Histone Acetyltransferases