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  • 1.
    Johnsson, Anna
    et al.
    Södertörn University, School of Life Sciences, Molecular biology. Karolinska Institutet.
    Durand-Dubief, Mickael
    Karolinska Intitutet.
    Xue-Franzen, Yongtao
    Södertörn University, School of Life Sciences, Molecular biology. Karolinska Institutet.
    Rönnerblad, Michelle
    Karolinska Institutet.
    Ekwall, Karl
    Södertörn University, School of Life Sciences, Molecular biology. Karolinska Institutet.
    Wright, Anthony P. H.
    Södertörn University, School of Life Sciences, Molecular biology. Karolinska Institutet.
    HAT-HDAC interplay modulates global histone H3K14 acetylation in gene-coding regions during stress2009In: EMBO Reports, ISSN 1469-221X, E-ISSN 1469-3178, Vol. 10, no 9, p. 1009-1014Article in journal (Refereed)
    Abstract [en]

    Histone acetylation and deacetylation are important for gene regulation. The histone acetyltransferase, Gcn5, is an activator of transcriptional initiation that is recruited to gene promoters. Here, we map genome-wide Gcn5 occupancy and histone H3K14ac at high resolution. Gcn5 is predominantly localized to coding regions of highly transcribed genes, where it collaborates antagonistically with the class-II histone deacetylase, Clr3, to modulate H3K14ac levels and transcriptional elongation. An interplay between Gcn5 and Clr3 is crucial for the regulation of many stress-response genes. Our findings suggest a new role for Gcn5 during transcriptional elongation, in addition to its known role in transcriptional initiation.

  • 2.
    Johnsson, Anna E.
    et al.
    Södertörn University, School of Life Sciences, Molecular biology.
    Wright, Anthony P. H.
    Södertörn University, School of Life Sciences, Molecular biology.
    The role of specific HAT-HDAC interactions in transcriptional elongation2010In: Cell Cycle, ISSN 1538-4101, E-ISSN 1551-4005, Vol. 9, no 3, p. 467-471Article in journal (Refereed)
    Abstract [en]

    We previously reported genome-wide evidence that the Gcn5 histone cetyltransferase (HAT) is located in the transcribed region of highly xpressed genes and that it plays an important role in transcriptional longation in the fission yeast, Schizosaccharomyces pombe (EMBO Reports 009; 10: 1009-14). Furthermore, the specific interplay between Gcn5 and he Clr3 histone deacetylase (HDAC) controls the acetylation levels of ysine-14 in histone H3 in the same class of highly expressed genes. utants of histone H3 that cannot be acetylated at residue 14 show imilar stress phenotypes to those observed for mutants lacking Gcn5. In his Extra View article we review these findings in relation to related iterature and extend important aspects of the original study. Notably, cn5 and Gcn5-dependent acetylation of histone H3K14 tend to be more nriched in the upstream regions of genes that require Gcn5 for correct xpression compared to genes that are independent of Gcn5. This suggests critical role of Gcn5 in the transcriptional initiation of these enes. Gcn5 is however most highly enriched in the transcribed regions f these gene sets but there is no difference between Gcn5-dependent and cn5-independent gene sets. Thus we suggest that Gcn5 plays an important ut redundant role in the transcriptional elongation of these genes. The ir2 HDAC has a similar genomic localization and enzymatic activity to lr3. We studied gcn5 Delta sir2 Delta double mutants that do not show a uppressed phenotype in relation to gcn5 Delta single mutants, compared o gcn5 Delta clr3 Delta mutants that do, in order to better understand he specificity of the interplay between Gcn5 and Clr3. In some classes f non-highly expressed genes the clr3 Delta mutant tends to restore evels of histone H3K14 acetylation in the double mutant strain more ffectively than sir2 Delta.

  • 3.
    Johnsson, Anna
    et al.
    Södertörn University, School of Life Sciences, Molecular biology. Karolinska Institutet.
    Xue-Franzen, Yongtao
    Södertörn University, School of Life Sciences, Molecular biology. Karolinska Intitutet.
    Lundin, Maria
    Södertörn University, School of Life Sciences, Molecular biology. Karolinska Institutet.
    Wright, Anthony P. H.
    Södertörn University, School of Life Sciences, Molecular biology. Karolinska Institutet.
    Stress-specific role of fission yeast Gcn5 histone acetyltransferase in programming a subset of stress response genes2006In: Eukaryotic Cell, ISSN 1535-9778, E-ISSN 1535-9786, Vol. 5, no 8, p. 1337-1346Article in journal (Refereed)
    Abstract [en]

    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 CaCl2-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, Gen5-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.

  • 4.
    Nugent, Rebecca L.
    et al.
    University of Southern California.
    Johnsson, Anna
    Södertörn University, School of Life Sciences, Molecular biology. Karolinska Intitutet.
    Fleharty, Brian
    Stowers Institute for Medical Research.
    Gogol, Madelaine
    Stowers Institute for Medical Research.
    Xue-Franzen, Yongtao
    Södertörn University, School of Life Sciences, Molecular biology. Karolinska Institutet.
    Seidel, Chris
    Stowers Institute for Medical Research.
    Wright, Anthony P. H.
    Södertörn University, School of Life Sciences, Molecular biology. Karolinska Institutet.
    Forsburg, Susan L.
    University of Southern California.
    Expression profiling of S. pombe acetyltransferase mutants identifies redundant pathways of gene regulation2010In: BMC Genomics, E-ISSN 1471-2164, Vol. 11, article id 59Article in journal (Refereed)
    Abstract [en]

    Background: Histone acetyltransferase enzymes (HATs) are implicated in egulation of transcription. HATs from different families may overlap in arget and substrate specificity. esults: We isolated the elp3(+) gene encoding the histone cetyltransferase subunit of the Elongator complex in fission yeast and haracterized the phenotype of an Delta elp3 mutant. We examined genetic nteractions between Delta elp3 and two other HAT mutants, Delta mst2 nd Delta gcn5 and used whole genome microarray analysis to analyze heir effects on gene expression. onclusions: Comparison of phenotypes and expression profiles in single, ouble and triple mutants indicate that these HAT enzymes have verlapping functions. Consistent with this, overlapping specificity in istone H3 acetylation is observed. However, there is no evidence for verlap with another HAT enzyme, encoded by the essential mst1(+) gene.

  • 5.
    Xue-Franzen, Yongtao
    et al.
    Södertörn University, School of Life Sciences, Molecular biology. Karolinska Institutet.
    Johnsson, Anna
    Södertörn University, School of Life Sciences, Molecular biology. Karolinska Intitutet.
    Brodin, David
    Karolinska Institutet.
    Henriksson, Johan
    Södertörn University, School of Life Sciences, Molecular biology. Karolinska Institutet.
    Bürglin, Thomas R.
    Södertörn University, School of Life Sciences, Molecular biology. Karolinska Institutet.
    Wright, Anthony P. H.
    Södertörn University, School of Life Sciences, Molecular biology. Karolinska Institutet.
    Genome-wide characterisation of the Gcn5 histone acetyltransferase in budding yeast during stress adaptation reveals evolutionarily conserved and diverged roles2010In: BMC Genomics, E-ISSN 1471-2164, Vol. 11, article id 200Article in journal (Refereed)
    Abstract [en]

    Background: Gcn5 is a transcriptional coactivator with histone cetyltransferase activity that is conserved with regard to structure as ell as its histone substrates throughout the eukaryotes. Gene egulatory networks within cells are thought to be evolutionarily iverged. The use of evolutionarily divergent yeast species, such as S. erevisiae and S. pombe, which can be studied under similar nvironmental conditions, provides an opportunity to examine the nterface between conserved regulatory components and their cellular pplications in different organisms. esults: We show that Gcn5 is important for a common set of stress esponses in evolutionarily diverged yeast species and that the activity f the conserved histone acetyltransferase domain is required. We define group of KCl stress response genes in S. cerevisiae that are pecifically dependent on Gcn5. Gcn5 is localised to many Gcn5-dependent enes including Gcn5 repressed targets such as FLO8. Gcn5 regulates ivergent sets of KCl responsive genes in S. cerevisiae and S. pombe. enome-wide localization studies showed a tendency for redistribution of cn5 during KCl stress adaptation in S. cerevisiae from short genes to he transcribed regions of long genes. An analogous redistribution was ot observed in S. pombe. onclusions: Gcn5 is required for the regulation of divergent sets of Cl stress-response genes in S. cerevisiae and S. pombe even though it s required a common group of stress responses, including the response o KCl. Genes that are physically associated with Gcn5 require its ctivity for their repression or activation during stress adaptation, roviding support for a role of Gcn5 as a corepressor as well as a oactivator. The tendency of Gcn5 to re-localise to the transcribed egions of long genes during KCl stress adaptation suggests that Gcn5 lays a specific role in the expression of long genes under adaptive onditions, perhaps by regulating transcriptional elongation as has been een for Gcn5 in S. pombe. Interestingly an analogous redistribution of cn5 is not seen in S. pombe. The study thus provides important new nsights in relation to why coregulators like Gcn5 are required for the orrect expression of some genes but not others.

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