, Volume 119, Issue 1, pp 99–113 | Cite as

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

  • Corinna Schirling
  • Christiane Heseding
  • Franziska Heise
  • Dörthe Kesper
  • Ansgar Klebes
  • Ludger Klein-Hitpass
  • Andrea Vortkamp
  • Daniel Hoffmann
  • Harald Saumweber
  • Ann E. Ehrenhofer-Murray
Research Article


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.



trichostatin A


histone acetyltransferase


histone deacetylase



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.

Supplementary material

412_2009_247_Fig1_ESM.jpg (86 kb)
Supplementary Fig. 1

Ubiquitous expression of dTip60 RNA during embryogenesis. Lateral views of embryos hybridized with digoxigenin-labeled RNA probes of dTip60 in antisense (a, b) and, as a control, in sense (c, d) orientation. Enrichment of staining at mesoderm and endoderm is likely to be due to the thickness of tissue in these regions (JPEG 85 kb)

412_2009_247_Fig1_ESM.tif (7.1 mb)
High resolution (TIFF 7291 kb)
412_2009_247_Fig2_ESM.jpg (50 kb)
Supplementary Fig. 2

Comparison of the anti-dTip60 antibody with the respective preimmune serum. a, c DAPI staining, b staining with anti-dTip60, d staining with preimmune serum. Slides are from the same batch, and no image processing was used (JPEG 49 kb)

412_2009_247_Fig2_ESM.tif (911 kb)
High resolution (TIFF 911 kb)
412_2009_247_Fig3_ESM.jpg (86 kb)
Supplementary Fig. 3

Position of the dsRNA fragments used for dTip60-RNAi knock-down in SL2 cells, position of the dTip60 mRNA fragment measured by RT-PCR, and position of the fragments used for the UAS-dTip60-RNAi construct. The positions are indicated relative to the cDNA of dTip60, which is derived from the cDNA clone LD31064. Horizontal bars indicate the intron–exon borders. (JPEG 86 kb)

412_2009_247_Fig3_ESM.tif (7 mb)
High resolution (TIFF 7159 kb)


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Copyright information

© Springer-Verlag 2009

Authors and Affiliations

  • Corinna Schirling
    • 1
  • Christiane Heseding
    • 1
  • Franziska Heise
    • 1
  • Dörthe Kesper
    • 2
  • Ansgar Klebes
    • 4
  • Ludger Klein-Hitpass
    • 5
  • Andrea Vortkamp
    • 2
  • Daniel Hoffmann
    • 3
  • Harald Saumweber
    • 6
  • Ann E. Ehrenhofer-Murray
    • 1
  1. 1.Abteilung für Genetik, Zentrum für Medizinische BiotechnologieUniversität Duisburg-EssenEssenGermany
  2. 2.Abteilung für Entwicklungsbiologie, Zentrum für Medizinische BiotechnologieUniversität Duisburg-EssenEssenGermany
  3. 3.Abteilung für Bioinformatik, Zentrum für Medizinische BiotechnologieUniversität Duisburg-EssenEssenGermany
  4. 4.Institut für Biologie-GenetikFreie Universität BerlinBerlinGermany
  5. 5.Institut für ZellbiologieUniversitätsklinikumEssenGermany
  6. 6.Abteilung Zytogenetik, Institut für BiologieHumboldt Universität BerlinBerlinGermany

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