Rhythmic profiles of cell cycle and circadian clock genes' transcripts in mice: a possible association between two periodic systems

Abstract

Summary The circadian system shapes the rhythms of most biological functions. The regulation of the cell cycle by a circadian clock was suggested to operate via stages S, G2, and G2/M. This study investigated a possible time link at stages G1 and G1/S as well. The daily expression profiles of cell cycle markers (Ccnd1, Ccne1 and Pcna) and circadian clock genes (Per2 and Clock) were monitored in liver and esophagus (low and high proliferation index, respectively) of BALB/c mice. Locomotor activity displayed a 24 hrs rhythm, establishing the circadian organization of the SCN. In the liver, the mRNA level patterns of Per2 and Clock fitted circadian rhythm with a 7:30 h shift. That temporal pattern suggests that the liver harbor a functional circadian clock. The rhythm of the analyzed cell cycle genes, however, were of low significance fitness and an opposite peak time between Pcna and Clock. These results propose a weak regulatory role of the circadian clock. In the esophagus, the rhythms of Clock and Per2 mRNA had a similar peak time and non circadian periods. Such results suggest that the esophagus either do not harbor a functional circadian apparatus or that phenotypes stem from differences in phase and amplitude of its various cell types' rhythms. The similarity in the rhythm parameters of Clock, Ccne1 and Pcna transcripts, questions the control of circadian clock upon the cell-cycle along G1 and G1/S stages. Yet G1/S transition may play a role in modulating the local clock of proliferating tissues.