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| Status |
Public on Sep 12, 2007 |
| Title |
Comparative Genomics Identifies Gene Targets for Retinoic Acid in the Embryonic Zebrafish Hearts |
| Organism |
Danio rerio |
| Experiment type |
Expression profiling by array
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| Summary |
Retinoic acid (RA) and 2,3,7,8-tetrachlorodibenzo-p-dioxin activate distinct ligand-dependent transcription factors, and both cause cardiac malformation and heart failure in zebrafish embryos. We hypothesized that they cause this response by hyperactivating a common set of genes critical for heart development. To test this, we used microarrays to measure transcripts changes in hearts isolated from zebrafish embryos 1,2,4 and 12 h after exposure to 1μM RA. We used hierarchical clustering to compare the transcriptional responses produced in the embryonic heart by RA and TCDD. We could identify no early responses in common between the two agents. However, at 12 h both treatments produced a dramatic downregulation of a common cluster of cell cycle progression genes, which we term the Cell Cycle Gene Cluster (CCGC). This was associated with a halt in heart growth. These results suggest that RA and TCDD ultimately trigger a common transcriptional response associated with heart failure, but not through the direct activation of a common set of genes. Among the genes rapidly induced by RA was Nr2F5, a member of the COUP-TF family of transcription repressors. We found that induction of Nr2F5 was both necessary and sufficient for the cardiotoxic response to RA.
Keywords: Comparative Genomics, Timecourse
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| Overall design |
For RA study, total of 24 samples were collected and analyzed by microarray. Samples of zebrafish embryonic hearts were collected at four timepoints: 1, 2, 4, 12 hours post RA dosing. For each timepoint, there are three replicates of microarray studies. Each replicate includes microarray studies of one sample of RA treated heats and one sample of vehicle control (DMSO) treated hearts.
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| Contributor(s) |
Chen J, Carney SA, Peterson RE, Heideman W |
| Citation(s) |
18230668 |
| Submission date |
Sep 12, 2007 |
| Last update date |
Jan 25, 2018 |
| Contact name |
Jing Chen |
| E-mail(s) |
chen12@wisc.edu
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| Phone |
6082624525
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| Organization name |
University of Wisconsin - Madison
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| Department |
pharmaceutical Sciences
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| Street address |
777 Highland Ave
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| City |
Madison |
| State/province |
WI |
| ZIP/Postal code |
53705 |
| Country |
USA |
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| Platforms (1) |
| GPL1319 |
[Zebrafish] Affymetrix Zebrafish Genome Array |
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| Samples (48)
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| GSM228871 |
embryonic hearts, RA treatment, T1h, biological replicate1 |
| GSM228872 |
embryonic hearts, RA treatment, T1h, biological replicate2 |
| GSM228873 |
embryonic hearts, RA treatment, T1h, biological replicate3 |
| GSM228874 |
embryonic hearts, DMSO treatment, T1h, biological replicate1 |
| GSM228875 |
embryonic hearts, DMSO treatment, T1h, biological replicate2 |
| GSM228876 |
embryonic hearts, DMSO treatment, T1h, biological replicate3 |
| GSM228877 |
embryonic hearts, RA treatment, T2h, biological replicate1 |
| GSM228878 |
embryonic hearts, RA treatment, T2h, biological replicate2 |
| GSM228879 |
embryonic hearts, RA treatment, T2h, biological replicate3 |
| GSM228880 |
embryonic hearts, DMSO treatment, T2h, biological replicate1 |
| GSM228881 |
embryonic hearts, DMSO treatment, T2h, biological replicate2 |
| GSM228882 |
embryonic hearts, DMSO treatment, T2h, biological replicate3 |
| GSM228883 |
embryonic hearts, RA treatment, T4h, biological replicate1 |
| GSM228884 |
embryonic hearts, RA treatment, T4h, biological replicate2 |
| GSM228885 |
embryonic hearts, RA treatment, T4h, biological replicate3 |
| GSM228886 |
embryonic hearts, DMSO treatment, T4h, biological replicate1 |
| GSM228887 |
embryonic hearts, DMSO treatment, T4h, biological replicate2 |
| GSM228888 |
embryonic hearts, DMSO treatment, T4h, biological replicate3 |
| GSM228889 |
embryonic hearts, RA treatment, T12h, biological replicate1 |
| GSM228890 |
embryonic hearts, RA treatment, T12h, biological replicate2 |
| GSM228891 |
embryonic hearts, RA treatment, T12h, biological replicate3 |
| GSM228892 |
embryonic hearts, DMSO treatment, T12h, biological replicate1 |
| GSM228893 |
embryonic hearts, DMSO treatment, T12h, biological replicate2 |
| GSM228894 |
embryonic hearts, DMSO treatment, T12h, biological replicate3 |
| GSM228895 |
embryonic hearts, TCDD treatment, T1h, biological replicate 1 |
| GSM228896 |
embryonic hearts, TCDD treatment, T1h, biological replicate 2 |
| GSM228897 |
embryonic hearts, TCDD treatment, T1h, biological replicate 3 |
| GSM228898 |
embryonic hearts, vehicle control treatment, T1h, biological replicate 1 |
| GSM228899 |
embryonic hearts, vehicle control treatment, T1h, biological replicate 2 |
| GSM228900 |
embryonic hearts, vehicle control treatment, T1h, biological replicate 3 |
| GSM228901 |
embryonic hearts, TCDD treatment, T 2h, biological replicate 1 |
| GSM228903 |
embryonic hearts, TCDD treatment, T 2h, biological replicate 2 |
| GSM228904 |
embryonic hearts, TCDD treatment, T 2h, biological replicate 3 |
| GSM228905 |
embryonic hearts, vehicle control treatment, T 2h, biological replicate1 |
| GSM228906 |
embryonic hearts, vehicle control treatment, T 2h, biological replicate2 |
| GSM228907 |
embryonic hearts, vehicle control treatment, T 2h, biological replicate3 |
| GSM228908 |
embryonic hearts, TCDD treatment, T 4h, biological replicate1 |
| GSM228909 |
embryonic hearts, TCDD treatment, T 4h, biological replicate2 |
| GSM228910 |
embryonic hearts, TCDD treatment, T 4h, biological replicate3 |
| GSM228911 |
embryonic hearts, vehicle control treatment, T 4h, biological replicate1 |
| GSM228912 |
embryonic hearts, vehicle control treatment, T 4h, biological replicate2 |
| GSM228913 |
embryonic hearts, vehicle control treatment, T 4h, biological replicate3 |
| GSM228914 |
embryonic hearts, TCDD treatment, T12h, biological replicate 1 |
| GSM228915 |
embryonic hearts, TCDD treatment, T12h, biological replicate 2 |
| GSM228916 |
embryonic hearts, TCDD treatment, T12h, biological replicate 3 |
| GSM228917 |
embryonic hearts, vehicle control treatment, T12h, biological replicate 1 |
| GSM228918 |
embryonic hearts, vehicle control treatment, T12h, biological replicate 2 |
| GSM228919 |
embryonic hearts, vehicle control treatment, T12h, biological replicate 3 |
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| Relations |
| BioProject |
PRJNA102513 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE9020_RAW.tar |
158.3 Mb |
(http)(custom) |
TAR (of CEL, EXP) |
| Processed data included within Sample table |
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