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

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.

ACKNOWLEDGMENTS

We are grateful to P. Maroy for the gift of the 1479/10 line, to N. Dos-Santos, E. Scola, A. Ikmi, D. Cohen, and J.-R. Huynh for their technical help, and to the Institut Pasteur Dynamic Imaging Platform for assistance and advice. We thank I. Boros, L. Tora, and A. Mazo for sharing data before publication, T. Grange and J. A. Lepesant for helpful discussions during the course of this work, and M. Buckingham, D. Fagegaltier, H. Thomassin, and L. Théodore for critical readings of the manuscript.

This work was supported by the Pasteur Institute and the C.N.R.S. (URA 2578) and by grants from the A.R.C. (7742/4383/3202). D.S. and C.C. were supported by the University of Paris VI and the Ministère de la Recherche.