Model based conjectures on mammalian clock controversies.
We explore some predictions of a previously developed detailed model of molecular timekeeping in mammals (Forger and Peskin, PNAS, 100:14806) in areas where our understanding of clock mechanisms are incomplete. It is conjectured that: (1) the clock's 24-h period depends on mRNA stability. (2) REV-ERBalpha suppresses and/or entrains rhythms in peripheral tissues by regulating CRY1 transcription. (3) CLK:BMAL1 oscillations are suppressed in the suprachiasmatic nuclei to enhance oscillations in other proteins. (4) PER2 is ineffective at causing phase advances because it is not induced by light during the late night. (5) The clock is a limit cycle oscillator that shows characteristics of the evening and morning oscillator model.
Forger
Daniel B
DB
Courant Institute of Mathematical Sciences, New York University, New York, NY 10012, USA. forger@post.harvard.edu
Peskin
Charles S
CS
D000818:Animals; D001683:Biological Clocks / Q000235:genetics* / Q000502:physiology; D018797:Cell Cycle Proteins; D056931:Cryptochromes; D004268:DNA-Binding Proteins / Q000502:physiology; D005420:Flavoproteins / Q000235:genetics; D008322:Mammals / Q000502:physiology*; D008957:Models, Genetic; D009687:Nuclear Proteins / Q000502:physiology; D056950:Period Circadian Proteins; D012333:RNA, Messenger / Q000502:physiology; D018160:Receptors, Cytoplasmic and Nuclear / Q000502:physiology; D014157:Transcription Factors
D018797:Cell Cycle Proteins; C538964:Cry1 protein, mouse; D056931:Cryptochromes; D004268:DNA-Binding Proteins; D005420:Flavoproteins; D009687:Nuclear Proteins; C513312:Per2 protein, mouse; D056950:Period Circadian Proteins; D012333:RNA, Messenger; D018160:Receptors, Cytoplasmic and Nuclear; D014157:Transcription Factors