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Molecular and Cellular Biology, April 2003, p. 2577-2586, Vol. 23, No. 7
0270-7306/03/$08.00+0     DOI: 10.1128/MCB.23.7.2577-2586.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.

DNA Hypermethylation in Drosophila melanogaster Causes Irregular Chromosome Condensation and Dysregulation of Epigenetic Histone Modifications{dagger}

Frank Weissmann,1 Inhua Muyrers-Chen,2 Tanja Musch,1 Dirk Stach,3 Manfred Wiessler,3 Renato Paro,2 and Frank Lyko1*

Research Group Epigenetics,1 Department of Molecular Toxicology, Deutsches Krebsforschungszentrum,3 ZMBH, University of Heidelberg, 69120 Heidelberg, Germany2

Received 3 September 2002/ Returned for modification 25 October 2002/ Accepted 8 January 2003

The level of genomic DNA methylation plays an important role in development and disease. In order to establish an experimental system for the functional analysis of genome-wide hypermethylation, we overexpressed the mouse de novo methyltransferase Dnmt3a in Drosophila melanogaster. These flies showed severe developmental defects that could be linked to reduced rates of cell cycle progression and irregular chromosome condensation. In addition, hypermethylated chromosomes revealed elevated rates of histone H3-K9 methylation and a more restricted pattern of H3-S10 phosphorylation. The developmental and chromosomal defects induced by DNA hypermethylation could be rescued by mutant alleles of the histone H3-K9 methyltransferase gene Su(var)3-9. This mutation also resulted in a significantly decreased level of genomic DNA methylation. Our results thus uncover the molecular consequences of genomic hypermethylation and demonstrate a mutual interaction between DNA methylation and histone methylation.

* Corresponding author. Mailing address: Deutsches Krebsforschungszentrum, Im Neuenheimer Feld 280, 69120 Heidelberg, Germany. Phone: 49 6221 42 3800. Fax: 49 6221 42 3802. E-mail: f.lyko{at}dkfz.de.

{dagger} This paper is dedicated to Harald zur Hausen on the occasion of his retirement as head of the German Cancer Research Center, with gratitude and appreciation for 20 years of leadership.

Molecular and Cellular Biology, April 2003, p. 2577-2586, Vol. 23, No. 7
0022-538X/03/$08.00+0     DOI: 10.1128/MCB.23.7.2577-2586.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.



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