Light induces chromatin modification in cells of the mammalian circadian clock.
The mammalian circadian clock resides in neurons of the hypothalamic suprachiasmatic nucleus (SCN). Light entrains phase resetting of the clock using the retino-hypothalamic tract, via release of glutamate. Nighttime light exposure causes rapid, transient induction of clock and immediate-early genes implicated in phase-shifting the pacemaker. Here we show that a nighttime light pulse caused phosphorylation of Ser10 in histone H3's tail, in SCN clock cells. The effect of light was specific, and the kinetics of H3 phosphorylation were characteristic of the early response, paralleling c-fos and Per1 induction. Using fos-lacZ transgenic mice, we found that H3 phosphorylation and Fos induction occurRed in the same SCN neurons. Systemic treatment with the GABAB receptor agonist baclofen prevented light-induced c-fos and Per1 expression and H3 phosphorylation, indicating that one signaling pathway governs both events. Our results suggest that dynamic chromatin remodeling in the SCN occurs in response to a physiological stimulus in vivo.
Crosio
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Institut de Génétique et de Biologie Moléculaire et Cellulaire, CNRS - INSERM - Université Louis Pasteur, 1 rue Laurent Fries, Illkirch-Strasbourg 67404, France.
Cermakian
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Allis
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Sassone-Corsi
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D000818:Animals; D001418:Baclofen / Q000494:pharmacology; D002843:Chromatin / Q000378:metabolism*; D002940:Circadian Rhythm / Q000187:drug effects / Q000235:genetics*; D058786:GABA-B Receptor Agonists; D017930:Genes, Reporter / Q000502:physiology; D006657:Histones / Q000378:metabolism*; D007763:Lac Operon / Q000502:physiology; D008027:Light; D051379:Mice; D009474:Neurons / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D010766:Phosphorylation / Q000187:drug effects; D010870:Pineal Gland / Q000166:cytology / Q000378:metabolism; D016760:Proto-Oncogene Proteins c-fos / Q000235:genetics; D018080:Receptors, GABA-B / Q000378:metabolism; D012160:Retina / Q000166:cytology / Q000378:metabolism; D013493:Suprachiasmatic Nucleus / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D013495:Supraoptic Nucleus / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D013997:Time Factors
D002843:Chromatin; D058786:GABA-B Receptor Agonists; D006657:Histones; D016760:Proto-Oncogene Proteins c-fos; D018080:Receptors, GABA-B; D001418:Baclofen