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.