|
| Status |
Public on Jul 29, 2019 |
| Title |
REV-ERBa and REV-ERBb function as key factors regulating Mammalian Circadian Output |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by high throughput sequencing
|
| Summary |
The circadian clock regulates behavioural and physiological processes in a 24-h cycle. The nuclear receptors REV-ERBa and REV-ERBb are involved in the cell-autonomous circadian transcriptional/translational feedback loops as transcriptional repressors. A number of studies have also demonstrated a pivotal role of REV-ERBs in regulation of metabolic, neuronal, and inflammatory functions including bile acid metabolism, lipid metabolism, and production of inflammatory cytokines. Given the multifunctional role of REV-ERBs, it is important to elucidate the mechanism through which REV-ERBs exert their functions. To this end, we established a Rev-erba/Rev-erbb double-knockout mouse embryonic stem (ES) cell model and analyzed the circadian clock and clock-controlled output gene expressions. A comprehensive mRNA-seq analysis revealed that the complete knockout of both Rev-erba and Rev-erbb does not abrogate expression rhythms of E-box-regulated core clock genes but drastically changes a diverse set of other rhythmically-expressed output genes. Of note, REV-ERBa/b deficiency does not compromise circadian expression rhythms of PER2, while REV-ERB target genes, Bmal1 and Npas2, are significantly upregulated. This study emphasizes REV-ERBs function to form an essential link between the circadian clock and a wide variety of cellular physiological functions.
|
| |
|
| Overall design |
Control (WT) and Rev-erba/Rev-erbb deficient (KO) mouse ES cells on Per2::Luciferase knock-in background were differentiated for 28 days upon embryoid body formation, treated with 100 nM dexamethasone, and subjected to RNA extraction at 4-h intervals from 12 h to 56 h after dexamethasone stimulation.
|
| |
|
| Contributor(s) |
Tsuchiya Y, Koike N, Yagita K |
| Citation(s) |
31308426 |
| Submission date |
Jan 25, 2019 |
| Last update date |
Jul 29, 2019 |
| Contact name |
Kazuhiro Yagita |
| E-mail(s) |
kyagita@koto.kpu-m.ac.jp
|
| Organization name |
Kyoto Prefectural University of Medicine
|
| Street address |
Kawaramachi-Hirokoji, Kamigyo-ku
|
| City |
Kyoto |
| ZIP/Postal code |
602-8566 |
| Country |
Japan |
| |
|
| Platforms (1) |
| GPL24247 |
Illumina NovaSeq 6000 (Mus musculus) |
|
| Samples (24)
|
|
| Relations |
| BioProject |
PRJNA517181 |
| SRA |
SRP182101 |
Less...
More...