Circadian regulation of cAMP response element-mediated gene expression in the suprachiasmatic nuclei

Karl Obrietan, Soren Impey, Dave Smith, Jaime Athos, Daniel R. Storm

Research output: Contribution to journalArticle

233 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Pages (from-to)17748-17756
Number of pages9
JournalJournal of Biological Chemistry
Volume274
Issue number25
DOIs
StatePublished - Jun 18 1999
Externally publishedYes

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Suprachiasmatic Nucleus
Response Elements
Gene expression
Gene Expression
Transcription
Reporter Genes
Clocks
Supraoptic Nucleus
Photic Stimulation
Circadian Clocks
Periodicity
Mitogen-Activated Protein Kinases
Cell Nucleus
Brain
Transcription Factors
Genes
Chemical activation
Experiments

ASJC Scopus subject areas

  • Biochemistry

Cite this

Circadian regulation of cAMP response element-mediated gene expression in the suprachiasmatic nuclei. / Obrietan, Karl; Impey, Soren; Smith, Dave; Athos, Jaime; Storm, Daniel R.

In: Journal of Biological Chemistry, Vol. 274, No. 25, 18.06.1999, p. 17748-17756.

Research output: Contribution to journalArticle

Obrietan, Karl ; Impey, Soren ; Smith, Dave ; Athos, Jaime ; Storm, Daniel R. / Circadian regulation of cAMP response element-mediated gene expression in the suprachiasmatic nuclei. In: Journal of Biological Chemistry. 1999 ; Vol. 274, No. 25. pp. 17748-17756.
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