The ecdysone receptor promotes or suppresses proliferation according to ligand level
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PROVIDER: PRJNA989161 | ENA |
REPOSITORIES: ENA
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Project description:Steroid hormones control various cellular activities in a context-dependent manner. For example, ecdysone, which acts through a type II nuclear receptor, has seemingly opposite effects in Drosophila wing precursors, promoting proliferation during larval stages, and triggering proliferation arrest at pupariation. We find that wing precursors proliferate normally in the complete absence of the ecdysone receptor (EcR), whether ecdysone is present or not, suggesting that ecdysone overrides a default anti-proliferative activity of the receptor. By contrast, termination of proliferation by high concentration of 20E at the end of larval life requires ligand-induced transcriptional activation by the receptor. The switch from one mode of regulation to the other is determined by ligand level, as measured with a calibrated EcR transcriptional reporter and ex vivo proliferation assays. Accordingly, RNA Seq analysis uncovers distinct transcriptional responses to different doses of ecdysone. Some genes are only activated at high doses (high threshold targets) and likely to comprise genes that stop proliferation at pupariation, when ecdysone titres are high. We find that other target genes respond to all physiological concentrations of ecdysone. Some of these genes are known to promote proliferation and could therefore contribute to the pro-proliferation activity of low-level ecdysone. Finally, we show mathematically and with synthetic reporters that relatively simple combinations of regulatory elements can recapitulate the behaviour of both types of target genes.
2023-08-24 | GSE236166 | GEO
Project description:The steroid hormone 20-hydroxy-ecdysone (20E) promotes proliferation in Drosophila wing precursors at low titer but triggers proliferation arrest at high doses. Remarkably, wing precursors proliferate normally in the complete absence of the 20E receptor, suggesting that low-level 20E promotes proliferation by overriding the default anti-proliferative activity of the receptor. By contrast, 20E needs its receptor to arrest proliferation. Dose-response RNA sequencing (RNA-seq) analysis of ex vivo cultured wing precursors identifies genes that are quantitatively activated by 20E across the physiological range, likely comprising positive modulators of proliferation and other genes that are only activated at high doses. We suggest that some of these "high-threshold" genes dominantly suppress the activity of the pro-proliferation genes. We then show mathematically and with synthetic reporters that combinations of basic regulatory elements can recapitulate the behavior of both types of target genes. Thus, a relatively simple genetic circuit can account for the bimodal activity of this hormone.
| S-EPMC7615657 | biostudies-literature
Project description:Pulses of the steroid hormone ecdysone act through transcriptional cascades to direct the major developmental transitions during the Drosophila life cycle. These include the prepupal ecdysone pulse, which occurs 10 hours after pupariation and triggers the onset of adult morphogenesis and larval tissue destruction. E93 encodes a transcription factor that is specifically induced by the prepupal pulse of ecdysone, supporting a model proposed by earlier work that it specifies the onset of adult development. Although a number of studies have addressed these functions for E93, little is known about its roles in the salivary gland where the E93 locus was originally identified. Here we show that E93 is required for development through late pupal stages, with mutants displaying defects in adult differentiation and no detectable effect on the destruction of salivary glands. RNA-seq analysis demonstrates that E93 regulates genes involved in development and morphogenesis in the salivary glands, but has little effect on cell death gene expression. We also show that E93 is required to direct the proper timing of ecdysone-regulated gene expression in salivary glands, and that it suppresses earlier transcriptional programs that occur during larval and prepupal stages. These studies support the model that the stage-specific induction of E93 in late prepupae provides a critical signal that defines the end of larval development and the onset of adult differentiation.
2022-08-11 | GSE181948 | GEO
Project description:Drosophila E93 promotes adult development and suppresses larval responses to ecdysone during metamorphosis
| PRJNA754032 | ENA
Project description:We used the DamID method to systematically identify the binding sites of Ecdysone Receptor and its heterodimeric partner USP across the whole genome in Drosophila Kc cells. We find that the EcR sites are a subset of the USP sites and that only a proportion are ecdysone regulated from an accompanying ecdysone profiling study. The role of EcR/USP in the ecdysone network appears to be coordinated by the recruitment of many transcription factors as well as signaling molecules. Keywords: DamID, chromatin profiling, DNA microarray
2008-05-01 | GSE9156 | GEO
Project description:Global quantitative proteomics reveals novel factors in the ecdysone signaling pathway in Drosophila melanogaster.
2015-01-23 | PXD001455 | Pride
Project description:Kc167 cells were mock-treated/treated with combinations of steroid hormone ecdysone and gamma-irradiation, and harvested. The expression profiles were determined using Affymetrix Drosophila Genechip 1 arrays. Comparisons between the sample groups allow the identification of genes with ecdysone- and/or radiation-responsive expression patterns. Experiment Overall Design: 1 set of control, ecdysone, gamma-irradiated, ecdysone + irradiated samples was analyzed.
2008-06-12 | E-GEOD-3072 | biostudies-arrayexpress
Project description:We used the DamID method to systematically identify the binding sites of Ecdysone Receptor and its heterodimeric partner USP across the whole genome in Drosophila Kc cells. We find that the EcR sites are a subset of the USP sites and that only a proportion are ecdysone regulated from an accompanying ecdysone profiling study. The role of EcR/USP in the ecdysone network appears to be coordinated by the recruitment of many transcription factors as well as signaling molecules. Keywords: DamID, chromatin profiling, DNA microarray In this study we mapped the genomic binding sites of steroid hormone nuclear receptor EcR and USP in Kc167 cells using the DamID method. DamID involves the low level expression of a fusion protein consisting of DNA adenine methyltransferase (Dam) and a chromatin protein of interest. This fusion protein is targeted to the native binding sites of the chromatin protein, where Dam methylates adenines in the surrounding DNA. The methylated DNA fragments were isolated and amplified by selective PCR, labeled with a fluorescent dye and hybridized to whole genome tiling microarrays. In this study,experiments were done with samples obtained from independent experiments and include dye swaps.
2008-05-01 | E-GEOD-9156 | biostudies-arrayexpress
Project description:Kc167 cells were mock-treated/treated with combinations of steroid hormone ecdysone and gamma-irradiation, and harvested. The expression profiles were determined using Affymetrix Drosophila Genechip 1 arrays. Comparisons between the sample groups allow the identification of genes with ecdysone- and/or radiation-responsive expression patterns. Keywords: response to hormone, stress response
2006-08-05 | GSE3072 | GEO
Project description:Here we examine changes in the distribution of Drosophila insulator proteins during the ecdysone response. We performed ChIP-seq analysis in Kc cells at 0, 3, and 48 hours of ecdysone treatment with antibodies against CP190, Su(Hw), dCTCF, and BEAF-32B. Examination of 4 different insulator proteins at 3 time points of ecdysone treatment.
2011-10-13 | E-GEOD-30740 | biostudies-arrayexpress