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J Biol Chem, Vol. 274, Issue 25, 17748-17756, June 18, 1999
From the Department of Pharmacology, University of Washington,
Seattle, Washington 98195-7280
A program of stringently-regulated gene
expression is thought to be a fundamental component of the circadian
clock. Although recent work has implicated a role for
E-box-dependent transcription in circadian rhythmicity, the
contribution of other enhancer elements has yet to be assessed. Here,
we report that cells of the suprachiasmatic nuclei (SCN) exhibit a
prominent circadian oscillation in cAMP response element (CRE)-mediated
gene expression. Maximal reporter gene expression occurred from
late-subjective night to mid-subjective day. Cycling of
CRE-dependent transcription was not observed in other brain
regions, including the supraoptic nucleus and piriform cortex. Levels
of the phospho-active form of the transcription factor CREB (P-CREB)
varied as a function of circadian time. Peak P-CREB levels occurred
during the mid- to late-subjective night. Furthermore, photic
stimulation during the subjective night, but not during the subjective
day, triggered a marked increase in CRE-mediated gene expression in the
SCN. Reporter gene experiments showed that activation of the p44/42
mitogen-activated protein kinase signaling cascade is required for
Ca2+-dependent stimulation of CRE-mediated
transcription in the SCN. These findings reveal the CREB/CRE
transcriptional pathway to be circadian-regulated within the SCN, and
raise the possibility that this pathway provides signaling information
essential for normal clock function.
Circadian Regulation of cAMP Response Element-mediated Gene
Expression in the Suprachiasmatic Nuclei
Copyright © 1999 by The American Society for Biochemistry and Molecular Biology, Inc.
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