REV-ERBα and REV-ERBβ function as key factors regulating Mammalian Circadian Output
| Autor: | Hitoshi Inokawa, Naoki Okubo, Hiroyoshi Fujiwara, Yuh Sasawaki, Toshikazu Kubo, Nobuya Koike, Yoshiki Tsuchiya, Kazuhiro Yagita, Tess Grieten, Kazuya Ikoma, Yasuhiro Umemura, Ryosuke Ikeda, Maho Inoue, Ryutaro Ono |
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| Rok vydání: | 2019 |
| Předmět: |
0301 basic medicine
Transcriptional Activation viruses Circadian clock lcsh:Medicine Gene Expression Receptors Cytoplasmic and Nuclear Biology Article Proinflammatory cytokine 03 medical and health sciences Mice 0302 clinical medicine Circadian Clocks Animals Circadian rhythms Circadian rhythm RNA Messenger lcsh:Science Embryonic Stem Cells Mammals Mice Knockout Multidisciplinary NPAS2 lcsh:R Lipid metabolism Cell biology Circadian Rhythm PER2 CLOCK Repressor Proteins 030104 developmental biology Nuclear receptor Gene Expression Regulation Nuclear Receptor Subfamily 1 Group D Member 1 lcsh:Q 030217 neurology & neurosurgery Transcription Factors |
| Zdroj: | Scientific Reports Scientific Reports, Vol 9, Iss 1, Pp 1-9 (2019) |
| ISSN: | 2045-2322 |
| Popis: | The circadian clock regulates behavioural and physiological processes in a 24-h cycle. The nuclear receptors REV-ERBα and REV-ERBβ 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-erbα/Rev-erbβ 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-erbα and Rev-erbβ 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-ERBα/β 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. |
| Databáze: | OpenAIRE |
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