| First Author | Ikeda R | Year | 2019 |
| Journal | Sci Rep | Volume | 9 |
| Issue | 1 | Pages | 10171 |
| PubMed ID | 31308426 | Mgi Jnum | J:283779 |
| Mgi Id | MGI:6388099 | Doi | 10.1038/s41598-019-46656-0 |
| Citation | Ikeda R, et al. (2019) REV-ERBalpha and REV-ERBbeta function as key factors regulating Mammalian Circadian Output. Sci Rep 9(1):10171 |
| abstractText | The circadian clock regulates behavioural and physiological processes in a 24-h cycle. The nuclear receptors REV-ERBalpha and REV-ERBbeta 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-erbalpha/Rev-erbbeta 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 double knockout of both Rev-erbalpha and Rev-erbbeta 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-ERBalpha/beta deficiency does not compromise circadian expression rhythms of PER2, while REV-ERB target genes, Bmal1 and Npas2, are significantly upregulated. This study highlight the relevance of REV-ERBs as pivotal output mediators of the mammalian circadian clock. |
