Differential control of Bmal1 circadian transcription by REV-ERB and ROR nuclear receptors.
Circadian rhythms result from feedback loops involving clock genes and their protein products. In mammals, 2 orphan nuclear receptors, REV-ERBalpha and RORalpha, 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 (alpha and beta) and ROR (alpha, beta, and gamma) 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.
Guillaumond
Fabienne
F
Douglas Hospital Research Centre, McGill University, 6875 LaSalle Blvd, Montreal, QC, Canada.
Dardente
Hugues
H
Giguère
Vincent
V
Cermakian
Nicolas
N
D056930:ARNTL Transcription Factors; D000818:Animals; D001483:Base Sequence; D051792:Basic Helix-Loop-Helix Proteins / Q000235:genetics / Q000378:metabolism*; D001683:Biological Clocks / Q000502:physiology; D002460:Cell Line; D002940:Circadian Rhythm / Q000502:physiology*; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D005786:Gene Expression Regulation; D017930:Genes, Reporter; D018257:Helix-Loop-Helix Motifs; D007668:Kidney / Q000502:physiology; D051379:Mice; D008810:Mice, Inbred C57BL; D008969:Molecular Sequence Data; D018482:Muscle, Skeletal / Q000502:physiology; D009154:Mutation; D018160:Receptors, Cytoplasmic and Nuclear / Q000235:genetics / Q000378:metabolism*; D011957:Receptors, Opioid / Q000235:genetics / Q000378:metabolism*; D016415:Sequence Alignment; D013950:Thymus Gland / Q000502:physiology; D014158:Transcription, Genetic
D056930:ARNTL Transcription Factors; D051792:Basic Helix-Loop-Helix Proteins; D004268:DNA-Binding Proteins; D018160:Receptors, Cytoplasmic and Nuclear; D011957:Receptors, Opioid; C538961:Bmal1 protein, mouse