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| Status |
Public on Nov 01, 2008 |
| Title |
Aryl Hydrocarbon Receptor Regulates Distinct Dioxin-Dependent and Dioxin-Independent Gene Batteries |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by array
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| Summary |
Conventional biochemical and molecular techniques identified previously several genes whose expression is regulated by the aryl hydrocarbon receptor (AHR). We sought to map the complete spectrum of AHR-dependent genes in male adult liver using expression arrays to contrast mRNA profiles in Ahr-null mice (Ahr–/–) with those in mice with wild-type AHR (Ahr+/+). Transcript profiles were determined both in untreated mice and in mice treated 19 h earlier with 1000 µg/kg 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). Expression of 456 ProbeSets was significantly altered by TCDD in an AHR-dependent manner, including members of the classic AHRE-I gene battery, such as Cyp1a1, Cyp1a2, Cyp1b1, and Nqo1. In the absence of exogenous ligand, AHR status alone affected expression of 392 ProbeSets, suggesting that the AHR has multiple functions in normal physiology. In Ahr–/– mice, only 32 ProbeSets exhibited responses to TCDD, indicating that the AHR is required for virtually all transcriptional responses to dioxin exposure in liver. The flavin-containing monooxygenases, Fmo2 and Fmo3, considered previously to be uninducible, were highly induced by TCDD in an AHR-dependent manner. The estrogen receptor alpha as well as two estrogen-receptor-related genes (alpha and gamma) exhibit AHR-dependent expression, thereby extending cross-talk opportunities between the intensively studied AHR and estrogen receptor pathways. p53 binding sites are over-represented in genes down-regulated by TCDD, suggesting that TCDD inhibits p53 transcriptional activity. Overall, our study identifies a wide range of genes that depend on the AHR, either for constitutive expression or for response to TCDD.
Keywords: treatment-control and mutant-wildtype
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| Overall design |
Mice bearing wild-type or genetically deleted AHRs were treated with corn oil vehicle or TCDD, and their livers analyzed by expression arrays.
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| Contributor(s) |
Boutros PC, Tijet N, Moffat ID, Okey AB, Tuomisto J, Pohjanvirta R |
| Citation(s) |
16214954 |
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| Submission date |
Jan 07, 2008 |
| Last update date |
Feb 11, 2019 |
| Contact name |
Paul C Boutros |
| E-mail(s) |
Paul.Boutros@utoronto.ca
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| Organization name |
Ontario Institute for Cancer Research
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| Street address |
101 College Street, Suite 800
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| City |
Toronto |
| State/province |
Ontario |
| ZIP/Postal code |
M5G 0A3 |
| Country |
Canada |
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| Platforms (1) |
| GPL1261 |
[Mouse430_2] Affymetrix Mouse Genome 430 2.0 Array |
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| Samples (17)
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| Relations |
| BioProject |
PRJNA108647 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE10082_RAW.tar |
1.2 Gb |
(http)(custom) |
TAR (of CEL, DAT, EXP) |
| Processed data included within Sample table |
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