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. 2006 Aug;5(8):1337-46.
doi: 10.1128/EC.00101-06.

Stress-specific role of fission yeast Gcn5 histone acetyltransferase in programming a subset of stress response genes

Anna Johnsson  1 , Yongtao Xue-Franzén, Maria Lundin, Anthony P H Wright
Affiliations

Stress-specific role of fission yeast Gcn5 histone acetyltransferase in programming a subset of stress response genes

Anna Johnsson et al. Eukaryot Cell. 2006 Aug.

Abstract

Gcn5 is a coactivator protein that contributes to gene activation by acetylating specific lysine residues within the N termini of histone proteins. Gcn5 has been intensively studied in the budding yeast, Saccharomyces cerevisiae, but the features of genes that determine whether they require Gcn5 during activation have not been conclusively clarified. To allow comparison with S. cerevisiae, we have studied the genome-wide role of Gcn5 in the distantly related fission yeast, Schizosaccharomyces pombe. We show that Gcn5 is specifically required for adaptation to KCl- and CaCl(2)-mediated stress in S. pombe. We have characterized the genome-wide gene expression responses to KCl stress and show that Gcn5 is involved in the regulation of a subset of stress response genes. Gcn5 is most clearly associated with KCl-induced genes, but there is no correlation between Gcn5 dependence and the extent of their induction. Instead, Gcn5-dependent KCl-induced genes are specifically enriched in four different DNA motifs. The Gcn5-dependent KCl-induced genes are also associated with biological process gene ontology terms such as carbohydrate metabolism, glycolysis, and nicotinamide metabolism that together constitute a subset of the ontology parameters associated with KCl-induced genes.

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Figures

FIG. 1.
FIG. 1.
Gcn5 is not required for normal growth. wt, wild type. (A) Fivefold dilutions of wild-type and gcn5− strains were spotted on rich medium (YEA) and the plates incubated at 30°C for 3 days. (B) Growth rate of log-phase wild-type (filled points) and gcn5− (clear points) cells in liquid culture (mean relative densities of three cultures ± standard deviations are plotted). (C) There is no morphological difference between wild-type and gcn5− cells in log phase. Cells were stained with Hoechst stain to visualize nuclear DNA. (D) gcn5 deletion causes small effects on gene expression. A scatter plot shows the mean signal intensity values of three independent microarray experiments. The flanking diagonal lines indicate a threshold value of a twofold change in expression (see Table S1 in the supplemental material for gene names, mean changes in induction [n-fold], and P values of the 260 genes with a reproducible change of >1.5-fold).
FIG. 2.
FIG. 2.
Gcn5 is required for growth under specific environmental stress conditions. The gcn5− mutant spotted on YEA plates at 36°C or YEA plates supplemented with 1 M KCl or 100 mM CaCl2 displayed reduced growth relative to the wild type (wt), whereas gcn5− mutant cells spotted on YEA plates supplemented with 1.2 M sorbitol showed no difference in growth from wild-type cells. Plates were incubated for 3 to 5 days at 25°C unless otherwise indicated.
FIG. 3.
FIG. 3.
Characterization of gene expression changes during the response to 1 M KCl. (A) Gene expression changes after 15-min KCl treatment are characterized by robust down-regulation of genes. A scatter plot of DNA microarray signal intensities after 15 min of KCl stress plotted against signal intensities of nonstressed control cells is shown. The flanking diagonal lines indicate a threefold change in expression. (B) Gene expression changes after 60 min of KCl treatment are characterized by robust up- and down-regulation of genes. A scatter plot of DNA microarray signal intensities after 60 min of KCl stress plotted against signal intensities of nonstressed control cells is shown. Annotations are as shown in panel A.
FIG. 4.
FIG. 4.
Gcn5 is required for regulation of a subset of genes involved in the KCl stress response. (A) Scatter plot showing an increase in the number of Gcn5-dependent genes and the extent of their dependence during KCl stress. n, number of genes with a mean change in induction of ≥2-fold (P ≤ 0.05). The mean change in induction (n-fold) for all genes in each class is indicated (dark line). (B) There is a significant overlap between genes involved in adaptation to KCl and genes with changed expression in the gcn5− mutant during KCl stress. A P of 0.00317 is the probability with which the observed overlap of 54 genes would be expected by chance. (C) KCl-induced genes show a significant overlap (P = 6.32 × 10−12) with genes that are dependent on Gcn5 during KCl adaptation. The overlaps (*) between genes with increased expression in the gcn5− mutant and KCl-repressed genes and between Gcn5-dependent genes and genes that are not involved in KCl adaptation were not considered significant (P > 0.05).
FIG. 5.
FIG. 5.
Identification of DNA sequence motifs that are specifically overrepresented in Gcn5-dependent KCl-induced genes. The bar charts show the frequency of four indicated DNA sequence motifs upstream (−800 bp from ATG) of genes within different classes relative to the genomic frequency of the motifs. The classes contain (i) 30 genes that are induced ≥2-fold after KCl treatment for 60 min, (ii) 52 genes that are induced ≥2-fold by KCl at 60 min but are not Gcn5 dependent (gcn5− NC; change in induction [n-fold] ≤ 1.1-fold), (iii) 27 genes that show reduced expression in the gcn5− mutant after 60 min of KCl treatment (≥2-fold) but are not KCl induced (KCl NC; change in induction [n-fold] ≤ 1.3-fold), and (iv) 9 × 30 randomly selected genes. The proportion (%) of genes in each class that contain each motif is indicated above the bars.
FIG. 6.
FIG. 6.
Gcn5-dependent KCl-induced genes are involved in similar biological processes. Relationships between GO processes enriched in the groups of KCl-induced genes (gray) and Gcn5-dependent genes (black) (Tables 3 and 4) are shown. Two GO processes are further enriched by Gcn5-dependent, KCl-induced genes (gray and black) (Table 3).
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