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| Status |
Public on Dec 22, 2011 |
| Title |
Cryptochromes mediate rhythmic repression of the glucocorticoid receptor |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by array
|
| Summary |
The circadian transcriptional repressors cryptochromes 1 (Cry1) and 2 (Cry2) interact with the C-terminus of the glucocorticoid receptor (GR) and are required for transrepression in response to the synthetic GR ligand dexamethasone (Dex) in mouse embryonic fibroblasts. Dex induction of many genes was increased in Cry-deficient fibroblasts suggesting that cryptochromes oppose transactivation in addition to contributing to transrepression. In mice, genetic loss of Cry1 and/or Cry2 resulted in glucose intolerance and constitutively high levels of circulating corticosterone, suggesting reduced glucocorticoid suppression of the hypothalamic-pituitary-adrenal axis coupled with increased sensitivity to the hyperglycemic effects of glucocorticoid-mediated transactivation in the liver. Cry1 and Cry2 association with a GRE in the Pck1 promoter was stimulated by Dex, and Dex-induced transcription of pck1 was strikingly increased in Cry-deficient livers. Finally, cry1-/-;cry2-/- mice subjected to 8 weeks of chronic Dex treatment exhibited incomplete suppression of circulating corticosterone and greater glucose intolerance compared with wildtype littermates subjected to the same chronic treatment, consistent with enhanced transcriptional response to the synthetic glucocorticoid ligand.
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| Overall design |
Total RNA was obtained from WT and Cry1/2 KO MEFs treated with Dexamethasone (1uM) or control EtOH for 16 hours.
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| Contributor(s) |
Yu RT, Lamia KA, Evans RM |
| Citation(s) |
22170608 |
| |
| Submission date |
Sep 30, 2010 |
| Last update date |
Jun 14, 2018 |
| Contact name |
Ruth T Yu |
| Organization name |
Salk Institute
|
| Department |
Gene Expression Lab
|
| Lab |
Ronald Evans
|
| Street address |
10010 N Torrey Pines Rd
|
| City |
La Jolla |
| State/province |
CA |
| ZIP/Postal code |
92037 |
| Country |
USA |
| |
|
| Platforms (1) |
| GPL6885 |
Illumina MouseRef-8 v2.0 expression beadchip |
|
| Samples (12)
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| Relations |
| BioProject |
PRJNA132767 |
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