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 Drosophila melanogaster dAda2a 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.

TAF10 and TAF10b partially redundant roles duringDrosophila melanogastermorphogenesis

“…[16][17][18] Recently, it has been reported that dTAF10 and dTAF10b have synergistic roles in the regulation of Drosophila morphogenesis and they are required for the activation of Halloween genes involved in ecdysone biosynthesis. [18][19][20] Taken together, these observations support the idea that functionally different TAFcontaining complexes participate in gene regulation.…”

Ligand-independent requirements of steroid receptors EcR and USP for cell survival

“…Absorbance was read at 450 nm using a MultiscanPlus II Spectrophotometer (Labsystems, Ramat-Gan, Israel). The ecdysteroid antiserum has the same affinity for ecdysone and 20E, 59 but because the standard curve was obtained with the latter, results are expressed as 20E equivalents.…”

Modularity of CHIP/LDB transcription complexes regulates cell differentiation

“…these two seemingly opposing roles are suggested to maintain the normal balance between the two forms of the hormone during fly development. 71 In conclusion, transcription co-factors such as ssDP, CHIP/LDB and LMo can exert profound effects on the function of the transcription factors they bind. the transcription complexes formed by these interactions are subjected to delicate regulation depending on availability of the co-factors.…”

“…Indeed, the two Drosophila Hat complexes, dataC and dsaGa, which share both the catalytic unit dGCn5 and the adaptor unit aDa3 but differ in the aDa2a or aDa2b subunits respectively, have very different effects on transcriptional gene regulation. [70][71][72] Interestingly, the dataC complex positively regulates genes that participate in the synthesis of the steroid hormone ecdysone in the prothoracic gland. In contrast, this complex negatively regulates the cells the LDB-Gata complex binds to the promoter of the P4.2 gene.…”