Affiliation:
1. 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
Abstract
ABSTRACT
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.
Publisher
American Society for Microbiology
Subject
Cell Biology,Molecular Biology
Cited by
87 articles.
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