Dataset Information


REV-ERB? and REV-ERB? function as key factors regulating Mammalian Circadian Output.

ABSTRACT: The circadian clock regulates behavioural and physiological processes in a 24-h cycle. The nuclear receptors REV-ERB? and REV-ERB? 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-erb?/Rev-erb? 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-erb? and Rev-erb? 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-ERB?/? 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.

PROVIDER: S-EPMC6629614 | BioStudies |

REPOSITORIES: biostudies

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2019-07-29 | GSE125696 | GEO