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 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.
Schirling
Corinna
C
Abteilung für Genetik, Zentrum für Medizinische Biotechnologie, Universität Duisburg-Essen, Universitätsstrasse 5, 45117, Essen, Germany.
Heseding
Christiane
C
Heise
Franziska
F
Kesper
Dörthe
D
Klebes
Ansgar
A
Klein-Hitpass
Ludger
L
Vortkamp
Andrea
A
Hoffmann
Daniel
D
Saumweber
Harald
H
Ehrenhofer-Murray
Ann E
AE
D000818:Animals; D004330:Drosophila / Q000196:embryology / Q000201:enzymology* / Q000235:genetics / Q000254:growth & development; D029721:Drosophila Proteins / Q000235:genetics / Q000378:metabolism*; D005786:Gene Expression Regulation; D049750:Genome, Insect; D051548:Histone Acetyltransferases / Q000235:genetics / Q000378:metabolism*; D021381:Protein Transport; D014921:Wings, Animal / Q000254:growth & development / Q000378:metabolism
D029721:Drosophila Proteins; D051548:Histone Acetyltransferases; C511056:Tip60 protein, Drosophila