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The orphan nuclear receptor REV-ERBalpha controls circadian transcription within the positive limb of the mammalian circadian oscillator

Published in Cell. 2002, vol. 110, no. 2, p. 251-260
Abstract Mammalian circadian rhythms are generated by a feedback loop in which BMAL1 and CLOCK, players of the positive limb, activate transcription of the cryptochrome and period genes, components of the negative limb. Bmal1 and Per transcription cycles display nearly opposite phases and are thus governed by different mechanisms. Here, we identify the orphan nuclear receptor REV-ERBalpha as the major regulator of cyclic Bmal1 transcription. Circadian Rev-erbalpha expression is controlled by components of the general feedback loop. Thus, REV-ERBalpha constitutes a molecular link through which components of the negative limb drive antiphasic expression of components of the positive limb. While REV-ERBalpha influences the period length and affects the phase-shifting properties of the clock, it is not required for circadian rhythm generation.
Keywords ARNTL Transcription FactorsAnimalsBase SequenceBasic Helix-Loop-Helix Transcription FactorsBiological Clocks/physiologyCLOCK ProteinsCell Cycle ProteinsCircadian Rhythm/physiologyCryptochromesDNA, ComplementaryDNA-Binding Proteins/genetics/metabolism/physiologyDrosophila ProteinsEye ProteinsFlavoproteins/geneticsGene Expression RegulationHeartHumansLiverMiceMice, Inbred C57BLMice, KnockoutMolecular Sequence DataNuclear Proteins/genetics/metabolism/physiologyNuclear Receptor Subfamily 1, Group F, Member 1Nuclear Receptor Subfamily 1, Group F, Member 3Period Circadian ProteinsPhotoreceptor Cells, InvertebratePromoter Regions, GeneticRNA, MessengerRatsReceptors, Cytoplasmic and Nuclear/genetics/metabolism/physiologyReceptors, G-Protein-CoupledReceptors, Retinoic AcidReceptors, Thyroid HormoneResponse ElementsSuprachiasmatic NucleusTrans-Activators/genetics/metabolismTranscription Factors/geneticsTranscription, Genetic
PMID: 12150932
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PREITNER, Nicolas et al. The orphan nuclear receptor REV-ERBalpha controls circadian transcription within the positive limb of the mammalian circadian oscillator. In: Cell, 2002, vol. 110, n° 2, p. 251-260. doi: 10.1016/s0092-8674(02)00825-5 https://archive-ouverte.unige.ch/unige:43607

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Deposited on : 2014-12-17

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