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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

Common EcR and ecdysone sensitive target genes with identical expression responses, same polarity expression targets. a Hierarchical clustering revealed a subset of differentially expressed genes which share the same expression response, when either the hormone or the receptor are removed. Clear resolution of down-regulated and up-regulated nodes where observed. Panels B and C. show line graphs of gene expression changes of the common, same polarity target genes between WT to mutant categories. The down-regulated node (B) contains 204 genes that represent targets that are normally activated. The up-regulated node (C) contains 293 genes that represent targets that are normally repressed. This explicitly shows that the hormone and receptor simultaneously function as both an activation signal as well as a repression signal upon distinct subsets of target genes
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Fig2: Common EcR and ecdysone sensitive target genes with identical expression responses, same polarity expression targets. a Hierarchical clustering revealed a subset of differentially expressed genes which share the same expression response, when either the hormone or the receptor are removed. Clear resolution of down-regulated and up-regulated nodes where observed. Panels B and C. show line graphs of gene expression changes of the common, same polarity target genes between WT to mutant categories. The down-regulated node (B) contains 204 genes that represent targets that are normally activated. The up-regulated node (C) contains 293 genes that represent targets that are normally repressed. This explicitly shows that the hormone and receptor simultaneously function as both an activation signal as well as a repression signal upon distinct subsets of target genes

Mentions: For the M (regulation) and A (expression) values established between the two groups and displayed in the M–A scatter plots (Fig. 2 and supplemental Figs. 3, 4, 5, 6) the average regulation value (M) for each gene was calculated by subtracting the mean expression from the two groups (a mean M of 1 yields a twofold greater expression in group 1 compared to group 0). The average expression value (A) is simply the mean expression value for the gene. Groups for the overall ANOVA were separated into WT and mutant, including all mutant groups. Groups for the matched stage comparison were separated into lifecycle stage comparisons (“BG mutant vs. wild type at BG” and “WPP mutant vs. wildtype”).Fig. 2


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

Davis MB, Li T - Genes Genomics (2013)

Common EcR and ecdysone sensitive target genes with identical expression responses, same polarity expression targets. a Hierarchical clustering revealed a subset of differentially expressed genes which share the same expression response, when either the hormone or the receptor are removed. Clear resolution of down-regulated and up-regulated nodes where observed. Panels B and C. show line graphs of gene expression changes of the common, same polarity target genes between WT to mutant categories. The down-regulated node (B) contains 204 genes that represent targets that are normally activated. The up-regulated node (C) contains 293 genes that represent targets that are normally repressed. This explicitly shows that the hormone and receptor simultaneously function as both an activation signal as well as a repression signal upon distinct subsets of target genes
© Copyright Policy
Related In: Results  -  Collection

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getmorefigures.php?uid=PMC3585846&req=5

Fig2: Common EcR and ecdysone sensitive target genes with identical expression responses, same polarity expression targets. a Hierarchical clustering revealed a subset of differentially expressed genes which share the same expression response, when either the hormone or the receptor are removed. Clear resolution of down-regulated and up-regulated nodes where observed. Panels B and C. show line graphs of gene expression changes of the common, same polarity target genes between WT to mutant categories. The down-regulated node (B) contains 204 genes that represent targets that are normally activated. The up-regulated node (C) contains 293 genes that represent targets that are normally repressed. This explicitly shows that the hormone and receptor simultaneously function as both an activation signal as well as a repression signal upon distinct subsets of target genes
Mentions: For the M (regulation) and A (expression) values established between the two groups and displayed in the M–A scatter plots (Fig. 2 and supplemental Figs. 3, 4, 5, 6) the average regulation value (M) for each gene was calculated by subtracting the mean expression from the two groups (a mean M of 1 yields a twofold greater expression in group 1 compared to group 0). The average expression value (A) is simply the mean expression value for the gene. Groups for the overall ANOVA were separated into WT and mutant, including all mutant groups. Groups for the matched stage comparison were separated into lifecycle stage comparisons (“BG mutant vs. wild type at BG” and “WPP mutant vs. wildtype”).Fig. 2

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