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Differential Control of Bmal1 Circadian Transcription by REV-ERB and ROR Nuclear Receptors

Douglas Hospital Research Centre, McGill University, 6875 LaSalle Blvd, Montreal (QC), Canada

Hugues Dardente

Douglas Hospital Research Centre, McGill University, 6875 LaSalle Blvd, Montreal (QC), Canada

Vincent Giguère

Molecular Oncology Group, Royal Victoria Hospital, McGill University, 687 Pine Avenue West, Montreal (QC), Canada

Nicolas Cermakian

Douglas Hospital Research Centre, McGill University, 6875 LaSalle Blvd, Montreal (QC), Canada, nicolas.cermakian{at}mcgill.ca

Circadian rhythms result from feedback loops involving clock genes and their protein products. In mammals, 2 orphan nuclear receptors, REV-ERB and ROR, play important roles in the transcription of the clock gene Bmal1. The authors now considerably extend these findings with the demonstration that all members of the REV-ERB ( and ß) and ROR (, ß, and ) families repress and activate Bmal1 transcription, respectively. The authors further show that transcription of Bmal1 is the result of competition between REV-ERBs and RORs at their specific response elements (RORE). Moreover, they demonstrate that Reverb genes are similarly expressed in the thymus, skeletal muscle, and kidney, whereas Ror genes present distinct expression patterns. Thus, the results indicate that all members of the REV-ERB and ROR families are crucial components of the molecular circadian clock. Furthermore, their strikingly different patterns of expression in nervous and peripheral tissues provide important insights into functional differences between circadian clocks within the organism.

Key Words: Bmal1 • circadian clock • orphan nuclear receptor • REV-ERB • ROR • peripheral oscillators

Journal of Biological Rhythms, Vol. 20, No. 5, 391-403 (2005)
DOI: 10.1177/0748730405277232


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