Expression of the transcriptional coactivators CBP and p300 in the hamster suprachiasmatic nucleus: possible molecular components of the mammalian circadian clock.

Immediate early genes are expressed in the mammalian suprachiasmatic nucleus in response to photic information arriving from the retina at restricted times of the day, therefore their expression is regulated by the circadian biological clock. These light-induced genes are also activated by the phosphorylated form of CREB (pCREB) that binds to a cAMP response element upstream of the genes. The nuclear proteins CBP and p300 are known to be coactivators with pCREB in certain cell types, but their identification within the rodent SCN has not been reported. Therefore, in this study we examined the distribution of both CBP and p300 in the hamster suprachiasmatic nucleus. CBP and p300 immunoreactivity is detected in cells throughout the suprachiasmatic nucleus, and the pattern of staining within cells is indicative of a nuclear location for these proteins. The number of cells immunoreactive for both CBP and p300 significantly decreases at mid-night circadian times with respect to mid-day circadian times, although the reduction is less than 20%. Neither CBP nor p300 expression is affected by a circadian phase-resetting light pulse given late in the night. The ability of CBP and p300 to interact with pCREB as well as with the clock gene BMAL1 is discussed, and we propose that CBP and p300 may interact with, and link, both clock genes and clock-controlled genes in the generation of circadian rhythms in mammals. We further suggest that there will be a general importance for the role of transcriptional coactivators such as CBP and p300 in many of the molecular pathways related to the mammalian circadian clock.