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| Status |
Public on Jun 17, 2022 |
| Title |
Next Generation Sequencing-based Quantitative Analysis of female whole body transcriptomes from w1118 (control) and foxo mutant flies exposed to normoxia or hypoxia for 16 hrs |
| Organism |
Drosophila melanogaster |
| Experiment type |
Expression profiling by high throughput sequencing
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| Summary |
Purpose: The goal of this RNA-Seq is to analyze the whole-body transcriptomes from normoxia vs hypoxia exposed flies to identify differentially expressed genes and to identify which differentially gene expression changes require the FOXO transcription factor
Abstract from associated manuscript: When exposed to low oxygen or hypoxia, animals must alter their metabolism and physiology to ensure proper cell-, tissue- and whole-body level adaptations to their hypoxic environment. These alterations often involve changes in gene expression. While extensive work has emphasized the importance of the HIF-1 alpha transcription factor on controlling hypoxia gene expression, less is known about other transcriptional mechanisms. We previously identified the transcription factor FOXO as a regulator of hypoxia tolerance in Drosophila larvae and adults. Here we use an RNA sequencing approach to identify FOXO-dependent changes in gene expression that are associated with these tolerance effects. We found that hypoxia altered the expression of over 2000 genes and that approximately 40% of these gene expression changes required FOXO. We discovered that hypoxia exposure led to a FOXO-dependent increase in genes involved in cell signaling, such as kinases, GTPase regulators, and regulators of the Hippo/Yorkie pathway. Among these, we identified homeodomain-interacting protein kinase (Hipk) as being required for hypoxia survival. We also found that hypoxia suppresses the expression of genes involved in ribosome synthesis and egg production, and we showed that hypoxia suppresses tRNA synthesis and mRNA translation and reduces female fecundity. Among the downregulated genes, we discovered that FOXO was required for suppression of many ribosomal protein genes and genes involved in oxidative phosphorylation, pointing to a role for FOXO in limiting energetically costly processes such as protein synthesis and mitochondrial activity upon hypoxic stress. This work uncovers a widespread role for FOXO in mediating hypoxia changes in gene expression.
Results: RNA Seq differential expression analysis identified a significant (p<0.05,> 1.5 fold expression) change in 2835 transcripts, with 1602 transcripts showing reduced expression levels and 1233 transcripts with elevated expression levels.
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| Overall design |
For each condition (normoxia vs hypoxia, w111w vs foxo mutant ) there were 3-4 independent biological samples, each consisting of total RNA extracted from 5 adult female flies.
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| Contributor(s) |
Grewal SS |
| Citation(s) |
36200850 |
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| Submission date |
Jun 15, 2022 |
| Last update date |
Dec 15, 2022 |
| Contact name |
Savraj Grewal |
| E-mail(s) |
[email protected]
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| Organization name |
University of Calgary
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| Street address |
3330 Hospital Drive
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| City |
Calgary |
| State/province |
Alberta |
| ZIP/Postal code |
T2N 4N1 |
| Country |
Canada |
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| Platforms (1) |
| GPL19132 |
Illumina NextSeq 500 (Drosophila melanogaster) |
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| Samples (15)
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| Relations |
| BioProject |
PRJNA849605 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE206206_foxo_hypoxia_regulated_genes.xlsx |
426.8 Kb |
(ftp)(http) |
XLSX |
| GSE206206_merged.abundance.xlsx |
4.9 Mb |
(ftp)(http) |
XLSX |
| GSE206206_w1118_hypoxia_regulated_genes.xlsx |
369.6 Kb |
(ftp)(http) |
XLSX |
SRA Run Selector |
| Raw data are available in SRA |
| Processed data are available on Series record |
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