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Light induces chromatin modification in cells of the mammalian circadian clock

Nature Neuroscience volume 3, pages 1241–1247 (2000)Cite this article

Abstract

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.

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Figure 1: Time- and light-dependent phosphorylation of histone H3 in the suprachiasmatic nucleus.
Figure 2: Photic stimulation did not induce H3 phosphorylation in the pineal gland and in the retina.
Figure 3: Timing correlation of histone H3 phosphorylation and c-fos induction in the SCN.
Figure 4: Baclofen inhibits light-induced phosphorylation of histone H3 and induction of c-fos and Per1 gene expression in the SCN.
Figure 5: Baclofen induces histone H3 phosphorylation and c-fos expression in the supraoptic nuclei (SON) in a light-independent manner.

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Acknowledgements

We thank T. Curran for the fos-lacZ transgenic mouse line. We thank H. Tei for the mPer1 cDNA, J. L. Vonesch for advice with confocal microscopy, E. Borrelli for reading the manuscript and E. Heitz and M. Rastegar for technical assistance. We thank Z. Travnickova, D. Whitmore, N. Foulkes, M. Pando and all members of the Sassone-Corsi laboratory for discussions and help. C.C. is supported by a postdoctoral fellowship from the European Community and N.C. by a Human Frontier Science Program long-term fellowship and a Canadian Institutes of Health Research postdoctoral fellowship. This work was supported by grants from Centre National de la Recherche Scientifique, Institut National de la Santé et de la Recherche Médicale, Centre Hospitalier Universitaire Régional, Fondation de la Recherche Médicale, Université Louis Pasteur, Human Frontier Science Program, Organon (Akzo/Nobel) and Association pour la Recherche sur le Cancer.

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  1. Claudia Crosio and Nicolas Cermakian: The first two authors contributed equally to this work

Authors and Affiliations

  1. Institut de Génétique et de Biologie Moléculaire et Cellulaire, CNRS - INSERM - Université Louis Pasteur, 1 rue Laurent Fries, Illkirch-Strasbourg, 67404, France

    Claudia Crosio, Nicolas Cermakian & Paolo Sassone-Corsi

  2. Department of Biochemistry and Molecular Genetics, University of Virginia H.S.C., Box 800733, Charlottesville, 22908-0733, Virginia, USA

    C. David Allis

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Correspondence to Paolo Sassone-Corsi.

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Crosio, C., Cermakian, N., Allis, C. et al. Light induces chromatin modification in cells of the mammalian circadian clock. Nat Neurosci 3, 1241–1247 (2000). https://doi.org/10.1038/81767

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