Promotion of Cell Viability and Histone Gene Expression by the Acetyltransferase Gcn5 and the Protein Phosphatase PP2A in Saccharomyces cerevisiae
Autor: | Anne Lafon, Bryce A Mendelsohn, Emily L. Petty, Lorraine Pillus, Shannon L Tomlinson |
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Rok vydání: | 2016 |
Předmět: |
0301 basic medicine
Saccharomyces cerevisiae Proteins Cell Survival Saccharomyces cerevisiae Investigations Histones 03 medical and health sciences 0302 clinical medicine Gene expression Genetics Humans Protein Phosphatase 2 Gene Histone Acetyltransferases biology Acetylation Protein phosphatase 2 biology.organism_classification Chromatin DNA-Binding Proteins enzymes and coenzymes (carbohydrates) 030104 developmental biology Histone Acetyltransferase biology.protein Phosphorylation Protein Processing Post-Translational 030217 neurology & neurosurgery Protein Binding |
Zdroj: | Genetics. 203:1693-1707 |
ISSN: | 1943-2631 |
Popis: | Histone modifications direct chromatin-templated events in the genome and regulate access to DNA sequence information. There are multiple types of modifications, and a common feature is their dynamic nature. An essential step for understanding their regulation, therefore, lies in characterizing the enzymes responsible for adding and removing histone modifications. Starting with a dosage-suppressor screen in Saccharomyces cerevisiae, we have discovered a functional interaction between the acetyltransferase Gcn5 and the protein phosphatase 2A (PP2A) complex, two factors that regulate post-translational modifications. We find that RTS1, one of two genes encoding PP2A regulatory subunits, is a robust and specific high-copy suppressor of temperature sensitivity of gcn5∆ and a subset of other gcn5∆ phenotypes. Conversely, loss of both PP2ARts1 and Gcn5 function in the SAGA and SLIK/SALSA complexes is lethal. RTS1 does not restore global transcriptional defects in gcn5∆; however, histone gene expression is restored, suggesting that the mechanism of RTS1 rescue includes restoration of specific cell cycle transcripts. Pointing to new mechanisms of acetylation–phosphorylation cross-talk, RTS1 high-copy rescue of gcn5∆ growth requires two residues of H2B that are phosphorylated in human cells. These data highlight the potential significance of dynamic phosphorylation and dephosphorylation of these deeply conserved histone residues for cell viability. |
Databáze: | OpenAIRE |
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