Journal of Molecular Medicine

, Volume 82, Issue 4, pp 256–264 | Cite as

Day/night rhythms in gene expression of the normal murine heart

  • Tami Martino
  • Sara Arab
  • Marty Straume
  • Denise D. Belsham
  • Nazneen Tata
  • Fang Cai
  • Peter Liu
  • Maria Trivieri
  • Martin Ralph
  • Michael J. Sole
Original Article

Abstract

Molecular circadian oscillators have recently been identified in heart and many other peripheral organs; however, little is known about the physiologic significance of circadian gene cycling in the periphery. While general temporal profiles of gene expression in the heart have been described under constant lighting conditions, patterns under normal day/night conditions may be distinctly different. To understand how gene expression contributes to cardiac function, especially in human beings, it is crucial to examine these patterns in 24-h light and dark environments. High-density oligonucleotide microarrays were used to assess myocardial expression of 12,488 murine genes at 3-h intervals under the normal conditions of light and dark cycling. Variation in genetic activity was considerable, as 1,634 genes (~13% of genes analyzed) exhibited statistically significant changes across the 24-h cycle. Some genes exhibited rhythmic expression, others showed abrupt change at light-to-dark and dark-to-light transitions. Importantly, genes that exhibited significant cycling rhythms mapped to key biological pathways, including for example cardiac cellular growth and remodeling, as well as transcription, translation, mitochondrial respiration, and signaling pathways. Gene expression in the heart is remarkably different in the day versus the night. Some gene cycling may be driven by the central circadian pacemaker, while other changes appear to be responses to light and dark. This has important implications regarding our understanding of how the molecular physiology of the heart is controlled, including temporal patterns of organ growth, renewal, and disease, comparative gene expression, and the most appropriate times for administration of therapy.

Keywords

Gene expression Molecular biology Myocardium Physiology 

Notes

Acknowledgements

We thank A. Dupuis for consulting on statistical analyses, E. Cuckerman for technical assistance, and D. Black and A. Wagner for graphics assistance. We are grateful for the support of the A. Ephriam and Shirley Diamond Cardiomyopathy Research Fund, and a grant from the Heart and Stroke Foundation of Ontario (T4479). D.D.B. acknowledges support from the Natural Science and Engineering Research Council of Canada. P.L. is Polo Chair of the Heart and Stroke Foundation of Ontario. M.S. acknowledges support from the University of Virginia for both the Center for Biomathematical Technology and the Center for Biological Timing, as well as NSF, NIH, and NSBRI.

Supplementary material

Supplementary Data 1

ESM1.pdf (93 kb)
(PDF 94 KB)

Supplementary Data to Table 2

ESM.pdf (415 kb)
(PDF 1MB)

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Copyright information

© Springer-Verlag 2004

Authors and Affiliations

  • Tami Martino
    • 1
  • Sara Arab
    • 1
  • Marty Straume
    • 4
  • Denise D. Belsham
    • 2
  • Nazneen Tata
    • 1
  • Fang Cai
    • 2
  • Peter Liu
    • 1
  • Maria Trivieri
    • 1
  • Martin Ralph
    • 3
  • Michael J. Sole
    • 1
    • 5
  1. 1.Heart and Stroke Richard Lewar Centre of Excellence and Toronto General Hospital Research InstituteTorontoCanada
  2. 2.Department of PhysiologyUniversity of TorontoTorontoCanada
  3. 3.Departments of Psychology and ZoologyUniversity of TorontoTorontoCanada
  4. 4.Department of Internal Medicine, Division of Endocrinology and Metabolism, The Center for Biomathematical TechnologyUniversity of Virginia Health SystemCharlottesvilleUSA
  5. 5. 13-212a ENToronto General HospitalTorontoCanada

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