Chromosoma

, Volume 119, Issue 1, pp 99–113

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

DOI: 10.1007/s00412-009-0247-z

Cite this article as:
Schirling, C., Heseding, C., Heise, F. et al. Chromosoma (2010) 119: 99. doi:10.1007/s00412-009-0247-z
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Abstract

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.

Abbreviations

TSA

trichostatin A

HAT

histone acetyltransferase

HDAC

histone deacetylase

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)

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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)

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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)

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High resolution (TIFF 7159 kb)

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