Genes of the Ecdysone Biosynthesis Pathway Are Regulated by the dATAC Histone Acetyltransferase Complex in Drosophila

Abstract

Uncovering mechanisms that regulate ecdysone production is an important step toward understanding the regulation of insect metamorphosis and processes in steroid-related pathologies. We report here the transcriptome analysis of DrosophilamelanogasterdAda2a and dAda3 mutants, in which subunits of the ATAC acetyltransferase complex are affected. In agreement with the fact that these mutations lead to lethality at the start of metamorphosis, both the ecdysone levels and the ecdysone receptor binding to polytene chromosomes are reduced in these flies. The cytochrome genes (spookier, phantom, disembodied, and shadow) involved in steroid conversion in the ring gland are downregulated, while the gene shade, which is involved in converting ecdysone into its active form in the periphery, is upregulated in these dATAC subunit mutants. Moreover, driven expression of dAda3 at the site of ecdysone synthesis partially rescues dAda3 mutants. Mutants of dAda2b, a subunit of the dSAGA histone acetyltransferase complex, do not share phenotype characteristics and RNA profile alterations with dAda2a mutants, indicating that the ecdysone biosynthesis genes are regulated by dATAC, but not by dSAGA. Thus, we provide one of the first examples of the coordinated regulation of a functionally linked set of genes by the metazoan-specific ATAC complex.

We are grateful to Christen Mirth (Janelia Farm) for fly strains, to Christelle Thibault for carrying out the Affymetrix expression analyses, and to Gabriella Pankotai-Bodo and Zita Nagy for critically reading the manuscript.

Binational grants between Spain and Hungary (HH2006-0025) and Hungary and France (FR-33/08) provided support to B.G., L.T., and I.B. L.B. was supported by the Hungarian State Science Fund (OTKA PD72491). Research was supported by funds from the FRM and the European Community (HPRN-CT 00504228, STREP LSHG-CT-2004-502950, and EUTRACC LSHG-CT-2007-037445) and Réseau National des Génopoles (no. 260) and by INCA (2008-UBICAN) grants to L.T.; Spanish Ministry of Research BFU2006-10180 and TAF-CHROMATIN European Network MRTN-CT-2004-504288 grants to A.F. and I.B.; and the Hungarian State Science Fund (OTKA K77443) to I.B.