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Genetics. 2016 Aug;203(4):1693-707. doi: 10.1534/genetics.116.189506. Epub 2016 Jun 17.

Promotion of Cell Viability and Histone Gene Expression by the Acetyltransferase Gcn5 and the Protein Phosphatase PP2A in Saccharomyces cerevisiae.

Author information

1
Division of Biological Sciences, Molecular Biology, University of California, San Diego Moores Cancer Center, La Jolla, California 92093.
2
Division of Biological Sciences, Molecular Biology, University of California, San Diego Moores Cancer Center, La Jolla, California 92093 lpillus@ucsd.edu.

Abstract

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 PP2A(Rts1) 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.

KEYWORDS:

acetylation (IOC2, PAB1, RHO2, MED6, ZDS1, PP2AB56); chromatin; phosphorylation; transcription

PMID:
27317677
PMCID:
PMC4981271
DOI:
10.1534/genetics.116.189506
[Indexed for MEDLINE]
Free PMC Article

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