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Extensive and divergent circadian gene expression in liver and heart

A Corrigendum to this article was published on 08 August 2002


Many mammalian peripheral tissues have circadian clocks1,2,3,4; endogenous oscillators that generate transcriptional rhythms thought to be important for the daily timing of physiological processes5,6. The extent of circadian gene regulation in peripheral tissues is unclear, and to what degree circadian regulation in different tissues involves common or specialized pathways is unknown. Here we report a comparative analysis of circadian gene expression in vivo in mouse liver and heart using oligonucleotide arrays representing 12,488 genes. We find that peripheral circadian gene regulation is extensive (≥8–10% of the genes expressed in each tissue), that the distributions of circadian phases in the two tissues are markedly different, and that very few genes show circadian regulation in both tissues. This specificity of circadian regulation cannot be accounted for by tissue-specific gene expression. Despite this divergence, the clock-regulated genes in liver and heart participate in overlapping, extremely diverse processes. A core set of 37 genes with similar circadian regulation in both tissues includes candidates for new clock genes and output genes, and it contains genes responsive to circulating factors with circadian or diurnal rhythms.

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Figure 1: Temporal profiles of circadian gene expression in liver (a, b) and heart (c, d).
Figure 2: Global comparison of biological processes associated with the genes exhibiting circadian expression in liver and heart.
Figure 3: Temporal expression profiles of genes showing circadian regulation in both liver and heart.
Figure 4: Individual circadian expression profiles of selected genes from the set common to liver and heart.


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This work was supported by the Edward R. and Anne G. Lefler Center, Harvard Medical School and the National Eye Institute (C.J.W.), a Deutsche Forschungsgemeinschaft Postdoctoral Fellowship (K-F.S.), the National Institute of Child Health and Human Development (F.C.D. and N.V.), and the National Human Genome Research Institute (W.H.W.). We thank S. Meng and the Harvard Center for Genomics Research for technical assistance and M.-C. Kao for programming.

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Correspondence to Charles J. Weitz.

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Storch, KF., Lipan, O., Leykin, I. et al. Extensive and divergent circadian gene expression in liver and heart. Nature 417, 78–83 (2002).

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