REV-ERBα and REV-ERBβ function as key factors regulating Mammalian Circadian Output
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.
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Podrobná bibliografie
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Publikováno v
- Scientific reports
Ročník 9; číslo 1; s. 10171 - 9
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Hlavní autoři
-
Ikeda, Ryosuke,
Tsuchiya, Yoshiki,
Koike, Nobuya,
Umemura, Yasuhiro,
Inokawa, Hitoshi,
Ono, Ryutaro,
Inoue, Maho,
Sasawaki, Yuh,
Grieten, Tess,
Okubo, Naoki,
Ikoma, Kazuya,
Fujiwara, Hiroyoshi,
Kubo, Toshikazu,
Yagita, Kazuhiro
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Typ dokumentu
- Journal Article
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Jazyk
- English
-
Vydáno
-
London
Nature Publishing Group UK
15. 07. 2019
Nature Publishing Group
-
Témata
-
Bibliografie
- ObjectType-Article-1
SourceType-Scholarly Journals-1
ObjectType-Feature-2
content type line 23
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ISSN
- 2045-2322
2045-2322
-
DOI
- 10.1038/s41598-019-46656-0
