Widespread regulation of gene expression in the Drosophila genome by the histone acetyltransferase dTip60

The MYST histone acetyltransferase (HAT) dTip60 is part of a multimeric protein complex that unites both HAT and chromatin remodeling activities. Here, we sought to gain insight into the biological functions of dTip60. Strong ubiquitous dTip60 knock-down in flies was lethal, whereas knock-down in th...

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Bibliographic Details
Published in:Chromosoma 2010-02, Vol.119 (1), p.99-113
Main Authors: Schirling, Corinna, Heseding, Christiane, Heise, Franziska, Kesper, Dörthe, Klebes, Ansgar, Klein-Hitpass, Ludger, Vortkamp, Andrea, Hoffmann, Daniel, Saumweber, Harald, Ehrenhofer-Murray, Ann E
Format: Article
Language:English
Subjects:
Animal Genetics and Genomics
Animals
Biochemistry
Biomedical and Life Sciences
Cell Biology
Developmental Biology
Drosophila
Drosophila - embryology
Drosophila - enzymology
Drosophila - genetics
Drosophila - growth & development
Drosophila Proteins - genetics
Drosophila Proteins - metabolism
Eukaryotic Microbiology
Gene Expression Regulation
Genome, Insect
Histone Acetyltransferases - genetics
Histone Acetyltransferases - metabolism
Human Genetics
Life Sciences
Protein Transport
Research Article
Wings, Animal - growth & development
Wings, Animal - metabolism
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Summary:The MYST histone acetyltransferase (HAT) dTip60 is part of a multimeric protein complex that unites both HAT and chromatin remodeling activities. Here, we sought to gain insight into the biological functions of dTip60. Strong ubiquitous dTip60 knock-down in flies was lethal, whereas knock-down in the wing imaginal disk led to developmental defects in the wing. dTip60 localized to the nucleus in early embryos and was present in a large number of interbands on polytene chromosomes. Genome-wide expression analysis upon depletion of dTip60 in cell culture showed that it regulated a large number of genes in Drosophila, among which those with chromatin-related functions were highly enriched. Surprisingly, a significant portion of these genes were upregulated upon dTip60 loss, indicating that dTip60 has repressive as well as activating functions. dTip60 protein was directly located at promoter regions of a subset of repressed genes, suggesting a direct role in gene repression. Comparison of the gene expression signature of dTip60 downregulation with that of histone deacetylase inhibition with trichostatin A revealed a significant correlation, suggesting that the dTip60 complex recruits an HDAC-containing complex to regulate gene expression in the Drosophila genome.
ISSN:0009-5915
1432-0886
DOI:10.1007/s00412-009-0247-z