REGULATION OF CAMP RESPONSE ELEMENT-BINDING PROTEIN (CREB) BINDING INTHE MAMMALIAN CLOCK PACEMAKER BY LIGHT BUT NOT A CIRCADIAN CLOCK

Mammalian circadian rhythms are considered to be regulated by a clock pacemaker located in the suprachiasmatic nuclei (SCN) of the hypothala mus. The molecular mechanism of entrainment and oscillation of circadi an rhythm are not well understood but photic induction of immediate-ea rly gene (IEG) expression in the SCN is thought to play a role. Here w e show that under 12 h light:12 h dark (LD) condition, the cAMP respon se element binding protein (CREB) binding to cAMP responsive promoter element (CRE) of NMDAR1/zeta 1 promoter region in the SCN is higher du ring the light than the dark by electro-mobility shift assay (EMSA). W hen animals are placed in constant dark, CREB DNA binding activity in the SCN is low and does not vary with circadian time when compared wit h cortex nuclear extract as a control. Most significantly, photic indu ction of CREB binding activity in the SCN occurs at all circadian time s tested, indicating that CREB DNA binding in the SCN is not gated by the endogenous clock. These results implicate the role of CREB in phot ic neuronal signaling in the SCN and suggest that CREB DNA binding act ivities may not be regulated by a circadian clock.