Histone H3 specific acetyltransferases are essential for cell cycle progression.
Longstanding observations suggest that acetylation and/or amino-terminal tail structure of histones H3 and H4 are critical for eukaryotic cells. For Saccharomyces cerevisiae, loss of a single H4-specific histone acetyltransferase (HAT), Esa1p, results in cell cycle defects and death. In contrast, although several yeast HAT complexes preferentially acetylate histone H3, the ... catalytic subunits of these complexes are not essential for viability. To resolve the apparent paradox between the significance of H3 versus H4 acetylation, we tested the hypothesis that H3 modification is essential, but is accomplished through combined activities of two enzymes. We observed that Sas3p and Gcn5p HAT complexes have overlapping patterns of acetylation. Simultaneous disruption of SAS3, the homolog of the MOZ leukemia gene, and GCN5, the hGCN5/PCAF homolog, is synthetically lethal due to loss of acetyltransferase activity. This key combination of activities is specific for these two HATs because neither is synthetically lethal with mutations of other MYST family or H3-specific acetyltransferases. Further, the combined loss of GCN5 and SAS3 functions results in an extensive, global loss of H3 acetylation and arrest in the G(2)/M phase of the cell cycle. The strikingly similar effect of loss of combined essential H3 HAT activities and the loss of a single essential H4 HAT underscores the fundamental biological significance of each of these chromatin-modifying activities.
Mesh Terms:
Acetylation, Acetyltransferases, Blotting, Western, Catalysis, Cell Cycle, Crosses, Genetic, DNA-Binding Proteins, Flow Cytometry, Fungal Proteins, Genes, Essential, Genes, Lethal, Histone Acetyltransferases, Histones, Macromolecular Substances, Point Mutation, Protein Kinases, Saccharomyces cerevisiae, Saccharomyces cerevisiae Proteins, Substrate Specificity, Transcription Factors
Acetylation, Acetyltransferases, Blotting, Western, Catalysis, Cell Cycle, Crosses, Genetic, DNA-Binding Proteins, Flow Cytometry, Fungal Proteins, Genes, Essential, Genes, Lethal, Histone Acetyltransferases, Histones, Macromolecular Substances, Point Mutation, Protein Kinases, Saccharomyces cerevisiae, Saccharomyces cerevisiae Proteins, Substrate Specificity, Transcription Factors
Genes Dev.
Date: Dec. 01, 2001
PubMed ID: 11731478
View in: Pubmed Google Scholar
Download Curated Data For This Publication
18037
Switch View:
- Interactions 1