High impact information on Nr1d1

• Here, we identify the orphan nuclear receptor REV-ERBalpha as the major regulator of cyclic Bmal1 transcription [1].
• While REV-ERBalpha influences the period length and affects the phase-shifting properties of the clock, it is not required for circadian rhythm generation [1].
• Expression levels of Rev-erbalpha were higher at 0100 h than at 1300 h (P < 0.05), and immunohistochemistry revealed a strong expression of this transcription factor specifically in chromaffin cells of the adrenal medulla [2].
• Here we show that Rev-erbalpha dramatically represses the basal activity of the mouse Bmal1 gene promoter via two monomeric binding sites, both of which are required for repression and are conserved between mouse and human [3].
• We have cloned Rev-erb beta, a novel isoform of the Rev-erb alpha orphan nuclear receptor [4].

Biological context of Nr1d1

• Rev-erb alpha acts as a negative regulator of transcription binding to the same response element than another orphan nuclear receptor, ROR alpha [5].
• Future studies on a potential role of Rev-erb alpha on glucose homeostasis and/or inflammation control are thus warranted [5].
• Rev-erb alpha expression increases during adipocyte differentiation of 3T3-L1 cells and is induced by PPAR gamma activation in both 3T3-L1 cells in vitro and in rat adipose tissue in vivo via a direct repeat (DR2) in the Rev-erb alpha promoter [5].
• Here we show that the mouse Rev-erbalpha gene contains at least two binding regions for the transcriptional activators close to its previously identified promoter region and in its first intron [6].
• Moreover, it explains the rhythmic phenotype of Rev-erbalpha-/- mutant mice, where a positive feedback is missing [7].

Anatomical context of Nr1d1

• The role of the orphan nuclear receptor Rev-Erb alpha in adipocyte differentiation and function [5].
• Rev-erb alpha is highly expressed in adipose tissue, skeletal muscle, heart, liver and brain [5].
• The expression of clock-control genes, such as Bmal1 and Rev-erbalpha, also displays diurnal oscillations in the uterus, but not in bone [8].
• In experiments with cultured cells, we show here that GSK3beta phosphorylates and stabilizes the orphan nuclear receptor Rev-erbalpha, a negative component of the circadian clock [9].
• In the present study, transient cotransfection experiments in rat hepatocytes in primary culture and rabbit kidney RK13 cells demonstrated that overexpression of Rev-erbalpha specifically decreases basal and HNF-4 stimulated human apoC-III promoter activity [10].

Associations of Nr1d1 with chemical compounds

• The DNA binding domains of Rev-erb alpha and beta are highly related to each other and to the retinoic acid related orphan receptor (ROR)/RZR subfamily of nuclear receptors [4].
• Nuclear receptor Rev-erbalpha is a critical lithium-sensitive component of the circadian clock [9].

Other interactions of Nr1d1

• On the other hand, the expression levels of DBP and Rev-erbalpha mRNAs were blunted in Clock mutant mice not only under ad libitum but also under RF conditions [11].
• Meal timing reversed the chronic jet lag-induced alterations in Rev-erbalpha and Per2 expression in liver and of all three clock genes in tumor and slowed tumor growth [12].

Analytical, diagnostic and therapeutic context of Nr1d1

• In an attempt to understand the circadian regulation of the mouse Rev-erbalpha gene, we developed a screening technique for BMAL1 and CLOCK binding regions consisting of chromatin-immunoprecipitation [6].
• In the present study, the expression of Rev-erbalpha was investigated in the mouse brain by in situ hybridization using antisense cRNA probe [13].

References