title: The unfolded protein response represses differentiation through the RPD3-SIN3 histone deacetylase.
abstract: In Saccharomyces cerevisiae, splicing of HAC1 mRNA is initiated in response to the accumulation of unfolded proteins in the endoplasmic reticulum by the transmembrane kinase-endoribonuclease Ire1p. Spliced Hac1p (Hac1ip) is a negative regulator of differentiation responses to nitrogen starvation, pseudohyphal growth, and meiosis. Here we show that the RPD3-SIN3 histone deacetylase complex (HDAC), its catalytic activity, recruitment of the HDAC to the promoters of early meiotic genes (EMGs) by Ume6p, and the Ume6p DNA-binding site URS1 in the promoters of EMGs are required for nitrogen-mediated negative regulation of EMGs and meiosis by Hac1ip. Co-immunoprecipitation experiments demonstrated that Hac1ip can interact with the HDAC in vivo. Systematic analysis of double deletion strains revealed that HAC1 is a peripheral component of the HDAC. In summary, nitrogen-induced synthesis of Hac1ip and association of Hac1ip with the HDAC are physiological events in the regulation of EMGs by nutrients. These data also define for the first time a gene class that is under negative control by the UPR, and provide the framework for a novel mechanism through which bZIP proteins repress transcription.
authors.affiliation: Department of Biological Chemistry, University of Michigan Medical Center, Ann Arbor, MI, USA.
authors.forename: Martin
authors.initials: M
authors.lastname: Schröder
authors.forename: Robert
authors.initials: R
authors.lastname: Clark
authors.forename: Chuan Yin
authors.initials: CY
authors.lastname: Liu
authors.forename: Randal J
authors.initials: RJ
authors.lastname: Kaufman
mesh_terms: D001665:Binding Sites; D002454:Cell Differentiation; D004268:DNA-Binding Proteins / Q000378:metabolism; D005656:Fungal Proteins / Q000378:metabolism*; D017353:Gene Deletion; D015966:Gene Expression Regulation, Fungal; D005800:Genes, Fungal; D006655:Histone Deacetylases / Q000378:metabolism*; D008540:Meiosis; D008562:Membrane Glycoproteins / Q000378:metabolism; D008954:Models, Biological; D009584:Nitrogen / Q000378:metabolism; D011233:Precipitin Tests; D011401:Promoter Regions, Genetic; D017510:Protein Folding; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D012326:RNA Splicing; D012097:Repressor Proteins / Q000378:metabolism*; D012441:Saccharomyces cerevisiae / Q000235:genetics / Q000378:metabolism; D029701:Saccharomyces cerevisiae Proteins / Q000378:metabolism*; D056264:Sin3 Histone Deacetylase and Corepressor Complex; D014157:Transcription Factors / Q000378:metabolism*
chemical_list: D004268:DNA-Binding Proteins; D005656:Fungal Proteins; D008562:Membrane Glycoproteins; D012097:Repressor Proteins; D029701:Saccharomyces cerevisiae Proteins; D014157:Transcription Factors; C089979:UME6 protein, S cerevisiae; C082863:IRE1 protein, S cerevisiae; D017346:Protein Serine-Threonine Kinases; C071665:RPD3 protein, S cerevisiae; D006655:Histone Deacetylases; D056264:Sin3 Histone Deacetylase and Corepressor Complex; D009584:Nitrogen