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REV-ERBa and REV-ERBb function as key factors regulating Mammalian Circadian Output

ABSTRACT: REV-ERBa and REV-ERBb function as key factors regulating Mammalian Circadian Output

PROVIDER: PRJNA517181 | ENA |

REPOSITORIES: ENA

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REV-ERBa and REV-ERBb function as key factors regulating Mammalian Circadian Output

Project description:The circadian clock regulates behavioural and physiological processes in a 24-h cycle. The nuclear receptors REV-ERBa and REV-ERBb 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-erba/Rev-erbb 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 complete knockout of both Rev-erba and Rev-erbb 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-ERBa/b deficiency does not compromise circadian expression rhythms of PER2, while REV-ERB target genes, Bmal1 and Npas2, are significantly upregulated. This study emphasizes REV-ERBs function to form an essential link between the circadian clock and a wide variety of cellular physiological functions.

2019-07-29 | GSE125696 | GEO

REV-ERBa regulates TH17 cell development and autoimmunity

Project description:RORγt is well recognized as the lineage defining transcription factor for TH17 cell development. However, the cell-intrinsic mechanisms that negatively regulate TH17 cell development and autoimmunity remain poorly understood. Here we demonstrate that the transcriptional repressor REV-ERBa is exclusively expressed in TH17 cells, competes with RORγt for their shared DNA consensus sequence, and negatively regulates TH17 cell development via repression of genes traditionally characterized as RORγt-dependent, including Il17a. Deletion of REV-ERBa enhanced TH17-mediated pro-inflammatory cytokine expression, exacerbating experimental autoimmune encephalomyelitis (EAE) and colitis. Treatment with REV-ERB-specific synthetic ligands, which have similar phenotypic properties as RORγ modulators, suppressed TH17 cell development, was effective in colitis intervention studies, and significantly decreased the onset, severity, and relapse rate in several models of EAE without affecting thymic cellularity. Our results establish that REV-ERBa negatively regulates pro-inflammatory TH17 responses in vivo and identifies the REV-ERBs as potential targets for the treatment of TH17-mediated autoimmune diseases.

2018-12-19 | GSE122726 | GEO

Transcriptomic Analysis of Rev-erba Knockout vs. Wildtype Primary Myoblast

Project description:Identify signaling pathways that are differentially regulated by Rev-erba in myogenic prcursor cells

2018-02-17 | GSE110765 | GEO

HNF6 and Rev-erba Integrate Hepatic Lipid Metabolism By Overlapping and Distinct Transcriptional Mechanisms [ChIP-Seq]

Project description:We address the function of HNF6 in the mouse liver metabolism and Rev-erba cistrome We performed Rev-erba ChIP-seq in mouse livers at 5pm of the day and compared between WT and HNF6-depleted livers.

2016-06-29 | E-GEOD-83790 | biostudies-arrayexpress

KLF15 dependent REV-ERBa binding in the heart

Project description:By comparing the ChIPseq signal of REV_ERBa in control (Flox) and cardiomyocytic KLF15 knockout (cKO), we identified the KLF15 dependent REV-ERBa binding and repression in the heart. We further compared the differential binding sites to KLF15 binding site, using a FLAG tagged cardiomyocytic transgenic (cTG1) mice.

2015-12-30 | GSE73741 | GEO

The nuclear receptor REV-ERBa modulates Th17 cell differentiation and function by competing with RORgt

Project description:T helper 17 (Th17) cells produce interleukin-17 (IL-17) cytokines and drive inflammatory responses in autoimmune diseases such as multiple sclerosis and rheumatoid arthritis. The differentiation of Th17 cells is dependent on the retinoic acid receptor-related orphan nuclear receptor RORgt. Here we identify REV-ERBa (encoded by Nr1d1), a member of the nuclear hormone receptor family (NHR), as a transcriptional repressor that antagonizes RORgt function in Th17 cells. REV-ERBa binds to ROR response elements (RORE) in Th17 cells and inhibits the expression of RORgt-dependent genes such as Il17a and Il17f. Furthermore, elevated REV-ERBa expression or treatment with a synthetic REV-ERB agonist significantly delays the onset and impedes the progression of experimental autoimmune encephalomyelitis (EAE), a Th17 cell-mediated autoimmune disease. These results suggest that modulating REV-ERB activity may hold therapeutic potential for treatment of Th17 cell-mediated autoimmune diseases.

2019-08-16 | GSE72271 | GEO

HNF6 and Rev-erba Integrate Hepatic Lipid Metabolism By Overlapping and Distinct Transcriptional Mechanisms [Affymetrix]

Project description:We address the function of HNF6 in the mouse liver metabolism and Rev-erba cistrome

2016-06-29 | GSE83789 | GEO

HNF6 and Rev-erba Integrate Hepatic Lipid Metabolism By Overlapping and Distinct Transcriptional Mechanisms [ChIP-Seq]

Project description:We address the function of HNF6 in the mouse liver metabolism and Rev-erba cistrome

2016-06-29 | GSE83790 | GEO

HNF6 and Rev-erba Integrate Hepatic Lipid Metabolism By Overlapping and Distinct Transcriptional Mechanisms [Affymetrix]

Project description:We address the function of HNF6 in the mouse liver metabolism and Rev-erba cistrome We performed microarray in mouse livers at 5pm of the day and compared between WT and HNF6-depleted livers.

2016-06-29 | E-GEOD-83789 | biostudies-arrayexpress

REV-ERBa regulates TH17 cell development and autoimmunity

Project description:REV-ERBa regulates TH17 cell development and autoimmunity

| PRJNA506082 | ENA