[Synchronization and genetic redundancy in circadian clocks].
A network of feedback loops constitutes the basis for circadian timing in mammals. Complex transcriptional, post-transcriptional and post-translational events are also involved in the ticking of circadian clocks, allowing them to run autonomously with their characteristic, near-24h period. Central to the molecular mechanism is the CLOCK/BMAL1 heterodimer of transcription factors. Recent data using Clock knock-out mice however suggest that CLOCK may not be as mandatory as initially suggested from data gathered in the Clock mutant mouse model. Indeed, it appears that the Clock homolog Npas2 is able to functionally compensate for Clock genetic ablation. Furthermore, real-time imaging techniques using different clock genes knock-out lines established on a PER2 ::Luc knock-in background now demonstrate that persistent rhythmicity in the suprachiasmatic nuclei likely arises as a consequence of combined genetic redundancy and strong intercellular coupling, the latter characteristic being likely weakened in peripheral tissues such as liver or lung. The present review aims at summarizing current knowledge of the molecular basis of circadian clocks and possible differences between central and peripheral clocks in light of recent findings in Clock knock-out mice.
Dardente
Hugues
H
School of Biological Sciences, Zoology Building, Tillydrone Avenue, Aberdeen AB24 2TZ, Ecosse, Royaume-Uni. h.dardente@abdn.ac.uk
D056930:ARNTL Transcription Factors; D000818:Animals; D051792:Basic Helix-Loop-Helix Proteins / Q000737:chemistry / Q000172:deficiency / Q000235:genetics / Q000502:physiology; D001683:Biological Clocks / Q000235:genetics* / Q000502:physiology; D056926:CLOCK Proteins; D018797:Cell Cycle Proteins / Q000235:genetics / Q000502:physiology; D021081:Chronobiology Disorders / Q000235:genetics / Q000503:physiopathology; D002940:Circadian Rhythm / Q000235:genetics* / Q000502:physiology; D056931:Cryptochromes; D025461:Feedback, Physiological; D005420:Flavoproteins / Q000235:genetics / Q000502:physiology; D005786:Gene Expression Regulation; D006801:Humans; D008322:Mammals / Q000502:physiology; D051379:Mice; D018345:Mice, Knockout; D008954:Models, Biological; D009419:Nerve Tissue Proteins / Q000172:deficiency / Q000235:genetics / Q000502:physiology; D009687:Nuclear Proteins / Q000172:deficiency / Q000235:genetics / Q000502:physiology; D009928:Organ Specificity; D056950:Period Circadian Proteins; D010766:Phosphorylation; D011499:Protein Processing, Post-Translational; D013493:Suprachiasmatic Nucleus / Q000502:physiology; D015534:Trans-Activators / Q000737:chemistry / Q000172:deficiency / Q000235:genetics / Q000502:physiology; D014157:Transcription Factors / Q000172:deficiency / Q000235:genetics / Q000502:physiology
D056930:ARNTL Transcription Factors; D051792:Basic Helix-Loop-Helix Proteins; D056926:CLOCK Proteins; D018797:Cell Cycle Proteins; D056931:Cryptochromes; D005420:Flavoproteins; D009419:Nerve Tissue Proteins; D009687:Nuclear Proteins; D056950:Period Circadian Proteins; D015534:Trans-Activators; D014157:Transcription Factors; C538960:BMAL1 protein, human; C538961:Bmal1 protein, mouse; C491259:Npas2 protein, mouse; C513312:Per2 protein, mouse; C538943:CLOCK protein, human; C538944:Clock protein, mouse