|
| Status |
Public on Mar 29, 2012 |
| Title |
Integral roles for Rev-erb alpha and Rev-erb beta in the circadian clock function [ChIP_seq] |
| Organism |
Mus musculus |
| Experiment type |
Genome binding/occupancy profiling by high throughput sequencing
|
| Summary |
The circadian clock acts at the genomic level to coordinate internal behavioral and physiologic rhythms via the CLOCK-BMAL transcriptional heterodimer. Although the nuclear receptors REV-ERBα and β have been proposed to contribute to clock function, their precise roles and importance remain unresolved. To establish their regulatory potential we generated comparative cistromes of both Rev-erb isoforms, which revealed shared recognition at over ~50% of their total sites and extensive overlap with the master clock regulator Bmal. While Rev-erbα has been shown to directly regulate Bmal expression, the cistromic analysis reveals a more profound connection between Bmal and Rev-erbα and β regulatory circuits than previously suspected. Genes within the intersection of the Bmal and Rev-erb cistromes are highly enriched for both clock and metabolic functions. As predicted by the cistromic analysis, dual depletion of Rev-erbα/β function by creating double-knockout mice (DKOs) profoundly disrupted circadian expression of core clock and lipid homeostatic genes. As a result, DKOs show strikingly altered circadian wheel-running behavior and deregulated lipid metabolism. These data reveal an integral role of Rev-erbα/β in clock function as well as provide a cistromic basis for the integration of circadian rhythm and metabolism.
|
| |
|
| Overall design |
Identification of Reverb alpha and Reverb beta binding sites in mouse liver at ZT8
|
| |
|
| Contributor(s) |
Yu RT, Cho H, Evans RM |
| Citation(s) |
22460952 |
| Submission date |
Nov 29, 2011 |
| Last update date |
May 15, 2019 |
| 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) |
| GPL9250 |
Illumina Genome Analyzer II (Mus musculus) |
|
| Samples (3) |
|
| This SubSeries is part of SuperSeries: |
| GSE34020 |
Integral roles for Rev-erb alpha and Rev-erb beta in the circadian clock function |
|
| Relations |
| SRA |
SRP009472 |
| BioProject |
PRJNA156459 |
