title: Phosphoinositide [PI(3,5)P2] lipid-dependent regulation of the general transcriptional regulator Tup1.
abstract: Transcriptional activity of a gene is governed by transcriptional regulatory complexes that assemble/disassemble on the gene and control the chromatin architecture. How cytoplasmic components influence the assembly/disassembly of transcriptional regulatory complexes is poorly understood. Here we report that the budding yeast Saccharomyces cerevisiae has a chromatin architecture-modulating mechanism that is dependent on the endosomal lipid PI(3,5)P(2). We identified Tup1 and Cti6 as new, highly specific PI(3,5)P(2) interactors. Tup1--which associates with multiple transcriptional regulators, including the HDAC (histone deacetylase) and SAGA complexes--plays a crucial role in determining an activated or repressed chromatin state of numerous genes, including GAL1. We show that, in the context that the Gal4 activation pathway is compromised, PI(3,5)P(2) plays an essential role in converting the Tup1-driven repressed chromatin structure into a SAGA-containing activated chromatin structure at the GAL1 promoter. Biochemical and cell biological experiments suggest that PI(3,5)P(2) recruits Cti6 and the Cyc8-Tup1 corepressor complex to the late endosomal/vacuolar membrane and mediates the assembly of a Cti6-Cyc8-Tup1 coactivator complex that functions to recruit the SAGA complex to the GAL1 promoter. Our findings provide important insights toward understanding how the chromatin architecture and epigenetic status of a gene are regulated by cytoplasmic components.
authors.affiliation: Molecular Biology and Genetics, Cornell University, Ithaca, New York 14853, USA.
authors.forename: Bong-Kwan
authors.initials: BK
authors.lastname: Han
authors.forename: Scott D
authors.initials: SD
authors.lastname: Emr
mesh_terms: D002352:Carrier Proteins / Q000378:metabolism; D002467:Cell Nucleus / Q000378:metabolism; D003470:Culture Media; D004790:Enzyme Induction / Q000235:genetics; D005686:Galactokinase / Q000235:genetics / Q000378:metabolism; D015966:Gene Expression Regulation, Fungal; D009687:Nuclear Proteins / Q000378:metabolism*; D018129:Phosphatidylinositol Phosphates / Q000378:metabolism*; D017853:Phosphotransferases (Alcohol Group Acceptor) / Q000378:metabolism; D011401:Promoter Regions, Genetic; D017434:Protein Structure, Tertiary; D021381:Protein Transport; D012097:Repressor Proteins / Q000378:metabolism*; D012441:Saccharomyces cerevisiae / Q000201:enzymology / Q000235:genetics* / Q000378:metabolism*; D029701:Saccharomyces cerevisiae Proteins / Q000378:metabolism*; D015398:Signal Transduction; D013312:Stress, Physiological; D015534:Trans-Activators / Q000378:metabolism
chemical_list: D002352:Carrier Proteins; C488527:Cti6 protein, S cerevisiae; D003470:Culture Media; D009687:Nuclear Proteins; D018129:Phosphatidylinositol Phosphates; D012097:Repressor Proteins; C507785:SAGA complex, S cerevisiae; D029701:Saccharomyces cerevisiae Proteins; C066502:TUP1 protein, S cerevisiae; D015534:Trans-Activators; C106336:phosphatidylinositol 3,5-diphosphate; C095504:FAB1 protein, S cerevisiae; D017853:Phosphotransferases (Alcohol Group Acceptor); D005686:Galactokinase