Document Detail


Phosphoinositide [PI(3,5)P2] lipid-dependent regulation of the general transcriptional regulator Tup1.
MedLine Citation:
PMID:  21536737     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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:
Bong-Kwan Han; Scott D Emr
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Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  Genes & development     Volume:  25     ISSN:  1549-5477     ISO Abbreviation:  Genes Dev.     Publication Date:  2011 May 
Date Detail:
Created Date:  2011-05-03     Completed Date:  2011-06-24     Revised Date:  2011-11-01    
Medline Journal Info:
Nlm Unique ID:  8711660     Medline TA:  Genes Dev     Country:  United States    
Other Details:
Languages:  eng     Pagination:  984-95     Citation Subset:  IM    
Affiliation:
Molecular Biology and Genetics, Cornell University, Ithaca, New York 14853, USA.
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MeSH Terms
Descriptor/Qualifier:
Carrier Proteins / metabolism
Cell Nucleus / metabolism
Culture Media
Enzyme Induction / genetics
Galactokinase / genetics,  metabolism
Gene Expression Regulation, Fungal*
Nuclear Proteins / metabolism*
Phosphatidylinositol Phosphates / metabolism*
Phosphotransferases (Alcohol Group Acceptor) / metabolism
Promoter Regions, Genetic
Protein Structure, Tertiary
Protein Transport
Repressor Proteins / metabolism*
Saccharomyces cerevisiae / enzymology,  genetics*,  metabolism*
Saccharomyces cerevisiae Proteins / metabolism*
Signal Transduction
Stress, Physiological
Trans-Activators / metabolism
Chemical
Reg. No./Substance:
0/Carrier Proteins; 0/Cti6 protein, S cerevisiae; 0/Culture Media; 0/Nuclear Proteins; 0/Phosphatidylinositol Phosphates; 0/Repressor Proteins; 0/SAGA complex, S cerevisiae; 0/Saccharomyces cerevisiae Proteins; 0/TUP1 protein, S cerevisiae; 0/Trans-Activators; 0/phosphatidylinositol 3,5-diphosphate; EC 2.7.1.-/FAB1 protein, S cerevisiae; EC 2.7.1.-/Phosphotransferases (Alcohol Group Acceptor); EC 2.7.1.6/Galactokinase

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