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Molecular and Cellular Biology, September 2005, p. 8228-8238, Vol. 25, No. 18
0270-7306/05/$08.00+0     doi:10.1128/MCB.25.18.8228-8238.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.

The Histone H3 Acetylase dGcn5 Is a Key Player in Drosophila melanogaster Metamorphosis

Clément Carré,{dagger} Dimitri Szymczak,{dagger},{ddagger} Josette Pidoux, and Christophe Antoniewski*

Laboratory of Drosophila Genetics and Epigenetics, Department of Developmental Biology, CNRS URA 2578, Institut Pasteur, 25 rue du Docteur Roux, 75724 Paris Cedex 15, France

Received 20 April 2005/ Returned for modification 20 May 2005/ Accepted 22 June 2005

Although it has been well established that histone acetyltransferases (HATs) are involved in the modulation of chromatin structure and gene transcription, there is only little information on their developmental role in higher organisms. Gcn5 was the first transcription factor with HAT activity identified in eukaryotes. Here we report the isolation and characterization of Drosophila melanogaster dGcn5 mutants. Null dGcn5 alleles block the onset of both oogenesis and metamorphosis, while hypomorphic dGcn5 alleles impair the formation of adult appendages and cuticle. Strikingly, the dramatic loss of acetylation of the K9 and K14 lysine residues of histone H3 in dGcn5 mutants has no noticeable effect on larval tissues. In contrast, strong cell proliferation defects in imaginal tissues are observed. In vivo complementation experiments revealed that dGcn5 integrates specific functions in addition to chromosome binding and acetylation. Surprisingly, a dGcn5 variant protein with a deletion of the bromodomain, which has been shown to recognize acetylated histones, appears to be fully functional. Our results establish dGcn5 as a major histone H3 acetylase in Drosophila which plays a key role in the control of specific morphogenetic cascades during developmental transitions.


* Corresponding author. Mailing address: Laboratory of Drosophila Genetics and Epigenetics, Department of Developmental Biology, CNRS URA 2578, Institut Pasteur, 25 rue du Docteur Roux, 75724 Paris Cedex 15, France. Phone: 33 1 44 38 93 35. Fax: 33 1 40 61 39 18. E-mail: antoniew{at}pasteur.fr.

{dagger} These authors contributed equally to this work.

{ddagger} Present address: Laboratory of Polarity and Morphogenesis, Institut Jacques Monod, 75251 Paris Cedex 05, France.


Molecular and Cellular Biology, September 2005, p. 8228-8238, Vol. 25, No. 18
0022-538X/05/$08.00+0     doi:10.1128/MCB.25.18.8228-8238.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.




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