HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) Supplementary figures Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Web of Science (36) Citing Articles via Google Scholar Google Scholar Articles by Triqueneaux, G. Articles by Laudet, V. Search for Related Content PubMed PubMed Citation Articles by Triqueneaux, G. Articles by Laudet, V.

Laboratoire de Biologie Moléculaire et Cellulaire, CNRS UMR 5161, Ecole Normale Supérieur de Lyon, 46 allée d’Italie, 69364 Lyon cedex, France
¹ Howard Hughes Medical Institute, Northwestern University, Department of Neurobiology and Physiology, 2205 Tech Drive, Evanston, IL 60208, USA
² Laboratoire de Physiologie des Membranes Cellulaires, CNRS UMR 6078, Université de Nice-Sophia Antipolis, Chemin du Lazaret, 06 238 Villefranche-sur-mer, France

(Requests for offprints should be addressed to V Laudet; Email: Vincent.Laudet{at}ens-lyon.fr)

^* (G Triqueneaux and S Thenot contributed equally to this work)

Rev-erb 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-erb mRNA isoforms, namely Rev-erb1 and Rev-erb 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-erb1) and P2 (Rev-erb2) 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-erb gene. In line with these data Rev-erb 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-erb circadian gene expression in evolutionarily distant vertebrates and suggest a role for Rev-erb in the circadian clock output.

This article has been cited by other articles:

				V. T. Vasu, C. E. Cross, and K. Gohil Nr1d1, an Important Circadian Pathway Regulatory Gene, Is Suppressed By Cigarette Smoke in Murine Lungs Integr Cancer Ther, December 1, 2009; 8(4): 321 - 328. [Abstract] [PDF]

				M. Teboul, A. Grechez-Cassiau, F. Guillaumond, and F. Delaunay How nuclear receptors tell time J Appl Physiol, December 1, 2009; 107(6): 1965 - 1971. [Abstract] [Full Text] [PDF]

				J. Rambaud, G. Triqueneaux, I. Masse, B. Staels, V. Laudet, and G. Benoit Rev-erb{alpha}2 mRNA Encodes a Stable Protein with a Potential Role in Circadian Clock Regulation Mol. Endocrinol., May 1, 2009; 23(5): 630 - 639. [Abstract] [Full Text] [PDF]

				J.M. Fustin, J.S. O'Neill, M.H. Hastings, D.G. Hazlerigg, and H. Dardente Cry1 Circadian Phase in vitro: Wrapped Up with an E-Box J Biol Rhythms, February 1, 2009; 24(1): 16 - 24. [Abstract] [PDF]

				M. Teboul, F. Guillaumond, A. Grechez-Cassiau, and F. Delaunay Minireview: The Nuclear Hormone Receptor Family Round the Clock Mol. Endocrinol., December 1, 2008; 22(12): 2573 - 2582. [Abstract] [Full Text] [PDF]

				Q. J. Meng, A. McMaster, S. Beesley, W. Q. Lu, J. Gibbs, D. Parks, J. Collins, S. Farrow, R. Donn, D. Ray, et al. Ligand modulation of REV-ERB{alpha} function resets the peripheral circadian clock in a phasic manner J. Cell Sci., November 1, 2008; 121(21): 3629 - 3635. [Abstract] [Full Text] [PDF]

				S. Hummasti and P. Tontonoz Adopting New Orphans into the Family of Metabolic Regulators Mol. Endocrinol., August 1, 2008; 22(8): 1743 - 1753. [Abstract] [Full Text] [PDF]

				C. Fontaine, E. Rigamonti, B. Pourcet, H. Duez, C. Duhem, J.-C. Fruchart, G. Chinetti-Gbaguidi, and B. Staels The Nuclear Receptor Rev-erb{alpha} Is a Liver X Receptor (LXR) Target Gene Driving a Negative Feedback Loop on Select LXR-Induced Pathways in Human Macrophages Mol. Endocrinol., August 1, 2008; 22(8): 1797 - 1811. [Abstract] [Full Text] [PDF]

				T. P. Burris Nuclear Hormone Receptors for Heme: REV-ERB{alpha} and REV-ERB{beta} Are Ligand-Regulated Components of the Mammalian Clock Mol. Endocrinol., July 1, 2008; 22(7): 1509 - 1520. [Abstract] [Full Text] [PDF]

				H. Duez and B. Staels The nuclear receptors Rev-erbs and RORs integrate circadian rhythms and metabolism Diabetes and Vascular Disease Research, June 1, 2008; 5(2): 82 - 88. [Abstract] [PDF]

				A. Grechez-Cassiau, B. Rayet, F. Guillaumond, M. Teboul, and F. Delaunay The Circadian Clock Component BMAL1 Is a Critical Regulator of p21WAF1/CIP1 Expression and Hepatocyte Proliferation J. Biol. Chem., February 22, 2008; 283(8): 4535 - 4542. [Abstract] [Full Text] [PDF]

				W. Cai, J. Rambaud, M. Teboul, I. Masse, G. Benoit, J.-A. Gustafsson, F. Delaunay, V. Laudet, and I. Pongratz Expression Levels of Estrogen Receptor Are Modulated by Components of the Molecular Clock Mol. Cell. Biol., January 15, 2008; 28(2): 784 - 793. [Abstract] [Full Text] [PDF]

				S.-i. Nishio, T. Kakizawa, G. Chatelain, G. Triqueneaux, F. Brunet, J. Rambaud, T. Lamonerie, and V. Laudet OTX5 Regulates Pineal Expression of the Zebrafish REV-ERB{alpha} through a New DNA Binding Site Mol. Endocrinol., January 1, 2008; 22(1): 23 - 32. [Abstract] [Full Text] [PDF]

				T. Kakizawa, S.-i. Nishio, G. Triqueneaux, S. Bertrand, J. Rambaud, and V. Laudet Two differentially active alternative promoters control the expression of the zebrafish orphan nuclear receptor gene Rev-erb{alpha} J. Mol. Endocrinol., May 1, 2007; 38(5): 555 - 568. [Abstract] [Full Text] [PDF]

				G. Benoit, A. Cooney, V. Giguere, H. Ingraham, M. Lazar, G. Muscat, T. Perlmann, J.-P. Renaud, J. Schwabe, F. Sladek, et al. International Union of Pharmacology. LXVI. Orphan Nuclear Receptors Pharmacol. Rev., December 1, 2006; 58(4): 798 - 836. [Abstract] [Full Text] [PDF]

				C. H. Ko and J. S. Takahashi Molecular components of the mammalian circadian clock Hum. Mol. Genet., October 15, 2006; 15(suppl_2): R271 - R277. [Abstract] [Full Text] [PDF]

				L. Canaple, J. Rambaud, O. Dkhissi-Benyahya, B. Rayet, N. S. Tan, L. Michalik, F. Delaunay, W. Wahli, and V. Laudet Reciprocal Regulation of Brain and Muscle Arnt-Like Protein 1 and Peroxisome Proliferator-Activated Receptor {alpha} Defines a Novel Positive Feedback Loop in the Rodent Liver Circadian Clock Mol. Endocrinol., August 1, 2006; 20(8): 1715 - 1727. [Abstract] [Full Text] [PDF]

				S. Shimba, N. Ishii, Y. Ohta, T. Ohno, Y. Watabe, M. Hayashi, T. Wada, T. Aoyagi, and M. Tezuka Brain and muscle Arnt-like protein-1 (BMAL1), a component of the molecular clock, regulates adipogenesis PNAS, August 23, 2005; 102(34): 12071 - 12076. [Abstract] [Full Text] [PDF]

				L. Appelbaum, A. Anzulovich, R. Baler, and Y. Gothilf Homeobox-Clock Protein Interaction in Zebrafish: A SHARED MECHANISM FOR PINEAL-SPECIFIC AND CIRCADIAN GENE EXPRESSION J. Biol. Chem., March 25, 2005; 280(12): 11544 - 11551. [Abstract] [Full Text] [PDF]