PUBLICATION
The orphan receptor Rev-erb{alpha} gene is a target of the circadian clock pacemaker
- Authors
- Triqueneaux, G., Thenot, S., Kakizawa, T., Antoch, M.P., Safi, R., Takahashi, J.S., Delaunay, F., and Laudet, V.
- ID
- ZDB-PUB-041216-6
- Date
- 2004
- Source
- Journal of molecular endocrinology 33(3): 585-608 (Journal)
- Registered Authors
- Delaunay, Franck, Laudet, Vincent, Safi, Rachid, Takahashi, Joe, Triqueneaux, Gérard
- Keywords
- none
- MeSH Terms
-
- ARNTL Transcription Factors
- Animals
- Base Sequence
- Basic Helix-Loop-Helix Transcription Factors
- Biological Clocks/genetics
- Biological Clocks/physiology*
- CLOCK Proteins
- Cell Line
- Circadian Rhythm/genetics
- Circadian Rhythm/physiology*
- Dimerization
- Humans
- Mice
- Molecular Sequence Data
- Oncogene Proteins v-erbA/genetics*
- Promoter Regions, Genetic/genetics
- Protein Isoforms/genetics
- Protein Isoforms/metabolism
- Rats
- Response Elements/genetics
- Sequence Alignment
- Trans-Activators/genetics
- Trans-Activators/metabolism
- Transcription Factors/genetics
- Transcription Factors/metabolism
- Transcriptional Activation/genetics
- Zebrafish/genetics
- PubMed
- 15591021 Full text @ J. Mol. Endocrinol.
Citation
Triqueneaux, G., Thenot, S., Kakizawa, T., Antoch, M.P., Safi, R., Takahashi, J.S., Delaunay, F., and Laudet, V. (2004) The orphan receptor Rev-erb{alpha} gene is a target of the circadian clock pacemaker. Journal of molecular endocrinology. 33(3):585-608.
Abstract
Rev-erbalpha is a ubiquitously expressed orphan nuclear receptor which functions as a constitutive transcriptional repressor and is expressed in vertebrates according to a robust circadian rhythm. We report here that two Rev-erbalpha mRNA isoforms, namely Rev-erbalpha1 and Rev-erbalpha 2, are generated through alternative promoter usage and that both show a circadian expression pattern in an in vitro system using serum-shocked fibroblasts. Both promoter regions P1 (Rev-erbalpha1) and P2 (Rev-erbalpha2) contain several E-box DNA sequences which function as response elements for the core circadian-clock components: CLOCK and BMAL1. The CLOCK-BMAL1 heterodimer stimulates the activity of both P1 and P2 promoters in transient transfection assay by 3-6-fold. This activation was inhibited by the overexpression of CRY1, a component of the negative limb of the circadian transcriptional loop. Critical E-box elements were mapped within both promoters. This regulation is conserved in vertebrates since we found that the CLOCK-BMAL1 heterodimer also regulates the zebrafish Rev-erbalpha gene. In line with these data Rev-erbalpha circadian expression was strongly impaired in the livers of Clock mutant mice and in the pineal glands of zebrafish embryos treated with Clock and Bmal1 antisense oligonucleotides. Together these data demonstrate that CLOCK is a critical regulator of Rev-erbalpha circadian gene expression in evolutionarily distant vertebrates and suggest a role for Rev-erbalpha in the circadian clock output.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping