Abstract
Steroid hormone gene regulation is often depicted as a linear transduction of the signal, from molecule release to the gene level, by activation of a receptor protein after being bound by its steroid ligand. Such an action would require that the hormone be present and bound to the receptor in order to have target gene response. Here, we present data that presents a novel perspective of hormone gene regulation, where the hormone molecule and its receptor have exclusive target gene regulation function, in addition to the traditional direct target genes. Our study is the first genome-wide analysis of conditional mutants simultaneously modeling the steroid and steroid receptor gene expression regulation. We have integrated classical genetic mutant experiments with functional genomics techniques in the Drosophila melanogaster model organism, where we interrogate the 20-hydroxyecdysone signaling response at the onset of metamorphosis. Our novel catalog of ecdysone target genes illustrates the separable transcriptional responses among the hormone, the pre-hormone receptor and the post-hormone receptor. We successfully detected traditional ecdysone target genes as common targets and also identified novel sets of target genes which where exclusive to each mutant condition. Around 12 % of the genome responds to the ecdysone hormone signal at the onset of metamorphosis and over half of these are independent of the receptor. In addition, a significant portion of receptor regulated genes are differentially regulated by the receptor, depending on its ligand state. Gene ontology enrichment analyses confirm known ecdysone regulated biological functions and also validate implicated pathways that have been indirectly associated with ecdysone signaling.Electronic supplementary materialThe online version of this article (doi:10.1007/s13258-013-0061-0) contains supplementary material, which is available to authorized users.
Highlights
Steroid hormone signaling is one of the most critical mechanisms required for development and viability
We established a catalog of genes that are dynamically active across pupariation and we have termed these genes the ‘‘metamorphosis onset genes’’
With a 5 % False Discovery Rate (FDR) we find that of the 1,021 genes with significant changes across metamorphosis onset, 33 % of were down-regulated in the mutant condition and 67 % were up-regulated (Fig. 5a), indicating the majority of genes that respond to the hormone signal are repression targets or tightly regulated to control the magnitude of their expression
Summary
Steroid hormone signaling is one of the most critical mechanisms required for development and viability. Steroids control many spatiotemporal changes related to tissue function and morphology. They function in these roles for the duration of life as they are released at regimented intervals throughout the life cycle. While hormone related treatments are considered more beneficial than harmful for their specific purposes, adverse side effects on non-target (Africander et al 2011; Buijs et al 2008; Hospers et al 2008; Kim and Freedland 2010). While gene expression regulation is the key role of steroid signaling that has been most extensively studied to date, the dynamics of this regulation are still not fully understood
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
