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Genomic analysis of the ecdysone steroid signal at metamorphosis onset using ecdysoneless and EcR Drosophila melanogaster mutants.

Davis MB, Li T - Genes Genomics (2013)

Bottom Line: 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.

View Article: PubMed Central - PubMed

Affiliation: Department of Genetics, Coverdell Biomedical Research Center, University of Georgia, 500 DW Brooks Dr S 270C, Athens, GA 30602 USA.

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.

No MeSH data available.


Related in: MedlinePlus

Exclusive metamorphosis target genes, specific to either unliganded receptor, ligand bound receptor or hormone. Bar graphs display the fold changes of gene expression for target genes exclusive to each indicated mutant condition. These subsets are also dynamic in wild type expression (metamorphosis onset genes). The CS bars represent the normal gene expression change at the relevant stages (relative to mean expression across BG, CG, and WPP stages). a The most significant BG-EcR- exclusive target genes. Presence of both activation and repression targets suggest the BG, pre-hormone receptor does not solely play a repressive role, but is also necessary for active transcription. b Subset of target genes exclusive to removing the EcR at WPP. Removing the receptor at the WPP stage also results in most genes showing a reversal in normal expression changes. A few also have significant reverse polarity effects at this stage (arrows). c Subset of target genes exclusive to removing the 20 H ecdysone. It appears that removing the hormone at the WPP stage (ecd) results in most genes losing not only the normal expression change, compared to wild type of either repression or activation, but have significant reversed polarity effects in transcriptional activity at this stage (arrows)
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Fig6: Exclusive metamorphosis target genes, specific to either unliganded receptor, ligand bound receptor or hormone. Bar graphs display the fold changes of gene expression for target genes exclusive to each indicated mutant condition. These subsets are also dynamic in wild type expression (metamorphosis onset genes). The CS bars represent the normal gene expression change at the relevant stages (relative to mean expression across BG, CG, and WPP stages). a The most significant BG-EcR- exclusive target genes. Presence of both activation and repression targets suggest the BG, pre-hormone receptor does not solely play a repressive role, but is also necessary for active transcription. b Subset of target genes exclusive to removing the EcR at WPP. Removing the receptor at the WPP stage also results in most genes showing a reversal in normal expression changes. A few also have significant reverse polarity effects at this stage (arrows). c Subset of target genes exclusive to removing the 20 H ecdysone. It appears that removing the hormone at the WPP stage (ecd) results in most genes losing not only the normal expression change, compared to wild type of either repression or activation, but have significant reversed polarity effects in transcriptional activity at this stage (arrows)

Mentions: Intriguingly, there are 731 genes regulated by the hormone that are not regulated by the receptor overall. Most of these genes are not normally dynamic at the onset of metamorphosis and these most likely represent some downstream or pleiotropic physiological effects of removing the hormone or the ecd1 mutant itself. However, upon filtering, the subset of 178 genes within the metamorphosis gene list reflects genes that are responsive to the hormone and not to the receptor at the onset of metamorphosis. This exclusive set of hormone responsive genes includes metabolic and immune response genes Fig. 6c.Fig. 6


Genomic analysis of the ecdysone steroid signal at metamorphosis onset using ecdysoneless and EcR Drosophila melanogaster mutants.

Davis MB, Li T - Genes Genomics (2013)

Exclusive metamorphosis target genes, specific to either unliganded receptor, ligand bound receptor or hormone. Bar graphs display the fold changes of gene expression for target genes exclusive to each indicated mutant condition. These subsets are also dynamic in wild type expression (metamorphosis onset genes). The CS bars represent the normal gene expression change at the relevant stages (relative to mean expression across BG, CG, and WPP stages). a The most significant BG-EcR- exclusive target genes. Presence of both activation and repression targets suggest the BG, pre-hormone receptor does not solely play a repressive role, but is also necessary for active transcription. b Subset of target genes exclusive to removing the EcR at WPP. Removing the receptor at the WPP stage also results in most genes showing a reversal in normal expression changes. A few also have significant reverse polarity effects at this stage (arrows). c Subset of target genes exclusive to removing the 20 H ecdysone. It appears that removing the hormone at the WPP stage (ecd) results in most genes losing not only the normal expression change, compared to wild type of either repression or activation, but have significant reversed polarity effects in transcriptional activity at this stage (arrows)
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Related In: Results  -  Collection

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Fig6: Exclusive metamorphosis target genes, specific to either unliganded receptor, ligand bound receptor or hormone. Bar graphs display the fold changes of gene expression for target genes exclusive to each indicated mutant condition. These subsets are also dynamic in wild type expression (metamorphosis onset genes). The CS bars represent the normal gene expression change at the relevant stages (relative to mean expression across BG, CG, and WPP stages). a The most significant BG-EcR- exclusive target genes. Presence of both activation and repression targets suggest the BG, pre-hormone receptor does not solely play a repressive role, but is also necessary for active transcription. b Subset of target genes exclusive to removing the EcR at WPP. Removing the receptor at the WPP stage also results in most genes showing a reversal in normal expression changes. A few also have significant reverse polarity effects at this stage (arrows). c Subset of target genes exclusive to removing the 20 H ecdysone. It appears that removing the hormone at the WPP stage (ecd) results in most genes losing not only the normal expression change, compared to wild type of either repression or activation, but have significant reversed polarity effects in transcriptional activity at this stage (arrows)
Mentions: Intriguingly, there are 731 genes regulated by the hormone that are not regulated by the receptor overall. Most of these genes are not normally dynamic at the onset of metamorphosis and these most likely represent some downstream or pleiotropic physiological effects of removing the hormone or the ecd1 mutant itself. However, upon filtering, the subset of 178 genes within the metamorphosis gene list reflects genes that are responsive to the hormone and not to the receptor at the onset of metamorphosis. This exclusive set of hormone responsive genes includes metabolic and immune response genes Fig. 6c.Fig. 6

Bottom Line: 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.

View Article: PubMed Central - PubMed

Affiliation: Department of Genetics, Coverdell Biomedical Research Center, University of Georgia, 500 DW Brooks Dr S 270C, Athens, GA 30602 USA.

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.

No MeSH data available.


Related in: MedlinePlus