Widespread regulation of gene expression in the Drosophila genome by the histone acetyltransferase dTip60
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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.
We are indebted to Peter B. Becker and Gunter Reuter for reagents. Bodo M. H. Lange and Hannah Müller are gratefully acknowledged for advice concerning RNAi in Drosophila cultured cells. Lothar Vassen is thanked for advice on the analysis of microarray experiments. We further thank Irina Passow, Renate Gienap, and Christiane Vole for excellent technical assistance and the Ehrenhofer-Murray lab for many helpful discussions. This project was funded by the Max-Planck-Society and the University of Duisburg-Essen.
- R Development Core Team (2008) R: A language and environment for statistical computing. R Foundation for Statistical Computing, ViennaGoogle Scholar