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Atypical patterns of circadian clock gene expression in human peripheral blood mononuclear cells

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Abstract

Circadian (∼24 h) rhythms in physiology and behaviour are observed in all mammals, including humans. These rhythms are generated by circadian clocks located in the hypothalamus and also in most peripheral tissues. Clock genes are essential components of circadian clocks, and mutations or polymorphisms within several of them have been associated with circadian disorders in humans. However, information about human clock gene expression has remained very limited. Peripheral blood mononuclear cells (PBMCs) represent an ideal material to investigate non-invasively the human clock at the molecular level. In the present study, we analysed the expression of three key clock genes, PER2, BMAL1 and REV-ERBα in PBMCs from ten healthy humans over a 24-h cycle. PER2 and BMAL1 were found to oscillate throughout the light–dark cycle in all subjects. Interestingly, despite normal melatonin and cortisol secretion patterns, two groups of subjects could be distinguished with significantly different mean PER2 and BMAL1 acrophases. BMAL1 oscillated with approximately the same phase as PER2, instead of being anti-phasic as anticipated from data previously obtained in other peripheral tissues. Furthermore, this unusual phase relationship of PER2 and BMAL1 in human PBMCs was associated with a constant expression of REV-ERBα, a crucial regulator of BMAL1, which is highly rhythmic in many other systems. These results reveal the existence of different chronotypes of clock gene expression patterns and suggest specific regulatory mechanisms in human PBMCs.

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Abbreviations

PBMC:

Peripheral blood mononuclear cell

SCN:

Suprachiasmatic nuclei

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Acknowledgements

The authors thank Dr. A. Goldbeter for helpful discussion. This work was supported by Ministère de la Recherche (ACI 5125), Association pour la Recherche sur le Cancer (No. 3256), and Fondation pour la Recherche Médicale.

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Authors and Affiliations

  1. Université de Nice-Sophia Antipolis, CNRS FRE 2721, Parc Valrose, 06108, Nice Cedex 2, France

    Michèle Teboul & Franck Delaunay

  2. UFR Odontologie Nice Sophia Antipolis, Pôle universitaire St Jean D’Angely, 24 avenue des diables bleus, 06357, Nice Cedex 4, France

    Marie-Audrey Barrat-Petit

  3. Hôpital Paul Brousse, INSERM E 0354 Chronothérapeutique des cancers, and Université Paris XI, 14 Av. P.V. Couturier, 94800, Villejuif, France

    Xiao Mei Li & Francis Lévi

  4. Centre de médecine nucléaire, Hôpital Neurocardiologique, 59 Bd Pinel, 69677, Bron, France

    Bruno Claustrat

  5. Laboratoire d’oncopharmocologie, Centre Antoine-Lacassagne, 33 Av. de Valombrose, 06189, Nice Cedex 2, France

    Jean-Louis Formento & Gérard Milano

Authors
  1. Michèle Teboul
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  2. Marie-Audrey Barrat-Petit
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  3. Xiao Mei Li
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  4. Bruno Claustrat
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  5. Jean-Louis Formento
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  6. Franck Delaunay
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  7. Francis Lévi
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  8. Gérard Milano
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Corresponding author

Correspondence to Michèle Teboul.

Additional information

Michèle Teboul and Marie-Audrey Barrat-Petit contributed equally to this work

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Teboul, M., Barrat-Petit, MA., Li, X.M. et al. Atypical patterns of circadian clock gene expression in human peripheral blood mononuclear cells. J Mol Med 83, 693–699 (2005). https://doi.org/10.1007/s00109-005-0697-6

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  • DOI: https://doi.org/10.1007/s00109-005-0697-6

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