The Nuclear Receptor REV-ERBα Regulates Fabp7 and Modulates Adult Hippocampal Neurogenesis

Schnell, Anna; Chappuis, Sylvie; Schmutz, Isabelle; Brai, Emanuele; Ripperger, Jürgen A.; Schaad, Olivier; Welzl, Hans; Descombes, Patrick; Albèri, Lavinia; Albrecht, Urs

doi:10.1371/journal.pone.0099883

Cited by 97 publications

(78 citation statements)

References 66 publications

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“…We previously observed that Nr3c1 mRNA expression is downregulated in the suprachiasmatic nuclei (SCN) of Rev-erbα −/− mice compared to wild-type animals (Schnell et al, 2014). This prompted us to test a potential relationship between REV-ERBα and GR.…”

Section: Discussionmentioning

confidence: 99%

“…Transfection and luciferase reporter assays were performed with NIH3T3 cells according to Schnell et al (2014). The Bmal1 promoter region cloned into pGL3 were used as positive controls.…”

Section: Methodsmentioning

confidence: 99%

“…Rev-erbα ( Nr1d1 ) is expressed in a variety of tissue types, including brown fat, skeletal muscle and liver (Woldt et al, 2013; Everett and Lazar, 2014). In addition to its action in the circadian clock mechanism, REV-ERBα has been implicated in adipogenesis (Kumar et al, 2010; Laitinen et al, 2015), muscle differentiation (Downes et al, 1995), liver metabolism (Bugge et al, 2012; Cho et al, 2012) and neurogenesis (Schnell et al, 2014). …”

Section: Introductionmentioning

confidence: 99%

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REV-ERBα influences the stability and nuclear localization of the glucocorticoid receptor

Okabe

Chavan

Costa

et al. 2016

Journal of Cell Science

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REV-ERBα (encoded by Nr1d1) is a nuclear receptor that is part of the circadian clock mechanism and regulates metabolism and inflammatory processes. The glucocorticoid receptor (GR, encoded by Nr3c1) influences similar processes, but is not part of the circadian clock, although glucocorticoid signaling affects resetting of the circadian clock in peripheral tissues. Because of their similar impact on physiological processes, we studied the interplay between these two nuclear receptors. We found that REV-ERBα binds to the C-terminal portion and GR to the N-terminal portion of HSP90α and HSP90β, a chaperone responsible for the activation of proteins to ensure survival of a cell. The presence of REV-ERBα influences the stability and nuclear localization of GR by an unknown mechanism, thereby affecting expression of GR target genes, such as IκBα (Nfkbia) and alcohol dehydrogenase 1 (Adh1). Our findings highlight an important interplay between two nuclear receptors that influence the transcriptional potential of each other. This indicates that the transcriptional landscape is strongly dependent on dynamic processes at the protein level.

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Section: Discussionmentioning

confidence: 99%

“…Transfection and luciferase reporter assays were performed with NIH3T3 cells according to Schnell et al (2014). The Bmal1 promoter region cloned into pGL3 were used as positive controls.…”

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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REV-ERBα influences the stability and nuclear localization of the glucocorticoid receptor

Okabe

Chavan

Costa

et al. 2016

Journal of Cell Science

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“…FABP5- and FABP7-deficient mice have a high level of AEA and NAEs in the brain and show analgesia in inflammatory pain models [28]. FABP7 mRNA expression is known to be regulated by REV-ERBα, and FABP7 is highly expressed in KO mice [29]. Therefore, the excessive expression of FABP7 may have contributed to causing the mechanical nociceptive sensitivity change in the KO mice in the present study.…”

Section: Discussionmentioning

confidence: 76%

Mildly Increased Mechanical Nociceptive Sensitivity in REV-ERBα Knock-out Mice

Lee

Kim

et al. 2016

Exp Neurobiol

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Nociception is one of the most complex senses that is affected not only by external stimulation but also internal conditions. Previous studies have suggested that circadian rhythm is important in modulating nociception. REV-ERBα knock-out (KO) mice have disrupted circadian rhythm and altered mood-related phenotypes. In this study, we examined the role of REV-ERBα in inflammatory nociception. We found that the nociceptive sensitivity of KO mice was partially enhanced in mechanical nociception. However, this partial alteration was independent of the circadian rhythm. Taken together, deletion of REV-ERBα induced a mild change in mechanical nociceptive sensitivity but this alteration was not dependent on the circadian rhythm.

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“…To uncover temporal patterns of mRNA abundance, we performed k-means clustering on genes displaying statistically significant temporal expression, defined as follows: to identify genes displaying a statistically significant effect over time, we used a likelihood ratio test implemented by sleuth version 0.29.0 (57), comparing a 29 full model with a parameter for each time point plus a batch effect (i.e. t=[0, 3,6,12,18,24,27,30,36,42,48,54,60,66,72, 78] plus a batch effect) versus a null model with no time effect (i.e. only a batch effect).…”

Section: Clustering Of Mrna Profilesmentioning

confidence: 99%

Simple and complex interactions between sleep-wake driven and circadian processes shape daily genome regulatory dynamics in the mouse

Yeung

et al. 2019

Preprint

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The timing and duration of sleep results from the interaction between a sleepwake driven, or homeostatic, process (S) and a circadian process (C), and involves changes in gene expression and genomic regulation. Unraveling the respective contributions of S and C, and their interaction, to transcriptional and epigenomic regulatory dynamics requires sampling over time under unperturbed conditions and conditions of perturbed sleep. Here, we profiled mRNA expression and chromatin accessibility in the cerebral cortex of mice over a three-day period, including a 6-hour sleep deprivation (SD) on day two. Mathematical modeling established that a large proportion of rhythmic genes are actually governed by Process S with varying degrees of interaction with Process C, sometimes working in opposition. Remarkably, SD causes long-term effects on gene expression dynamics, outlasting phenotypic recovery, most strikingly illustrated by a dampening of the oscillation of most core clock genes, including Bmal1, suggesting that enforced wakefulness directly impacts the molecular clock machinery. Chromatin accessibility proved highly plastic and dynamically affected by SD. Distal regions, rather than promoters, display dynamics corresponding to gene transcription, implying that changes in mRNA expression result from constantly accessible promoters under the influence of distal enhancers or repressors. Srf was predicted as a transcriptional regulator driving immediate response, suggesting that Srf activity mirrors the build-up and release of sleep pressure. Our results demonstrate that a single, short SD has long-term aftereffects at the genomic regulatory level. Such effects might accumulate with repeated sleep restrictions, thereby contributing to their adverse health effects. Significance statementWhen and how long we sleep is determined by the time-of-day and how long we have been awake, which are tracked molecularly by a circadian and a sleep-wake driven process, respectively. We measured the long-term consequences of a short-term sleep deprivation (SD) on gene expression and regulation in the mouse brain, and used mathematical models to determine the relative contributions of the circadian and sleep-wake driven processes. We find that many genes, including most of the genes that constitute the molecular circadian clock, are perturbed by SD long after the mice ceased showing behavioral signs of sleep loss. Our results have implications for human health, given the high prevalence of insufficient and poor quality sleep in our contemporary society. 4

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The Nuclear Receptor REV-ERBα Regulates Fabp7 and Modulates Adult Hippocampal Neurogenesis

Cited by 97 publications

References 66 publications

REV-ERBα influences the stability and nuclear localization of the glucocorticoid receptor

REV-ERBα influences the stability and nuclear localization of the glucocorticoid receptor

Mildly Increased Mechanical Nociceptive Sensitivity in REV-ERBα Knock-out Mice

Simple and complex interactions between sleep-wake driven and circadian processes shape daily genome regulatory dynamics in the mouse

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