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Discovery of circadian harmonics


We profiled global gene expression over two full days using Affymetrix microarrays. We identified rhythmic transcripts in the mouse liver and pituitary, as well as fibroblasts (NIH3T3) and osteosarcoma cells (U2OS). To our surprise, we found several hundred genes cycling with period lengths much shorter than 24 hours. These ultradian rhythms had period lengths of ~8 and ~12 hours -- i.e., the second and third harmonics of the core circadian oscillation.

Subsequently, we have shown that these rhythms are found in tissues throughout the body. Moreover, they are found in fruit flies as well, suggesting that circadian harmonics are a common feature of animal transcriptional rhythms. At a mechanistic level, 12 hour rhythms require both a central and peripheral circadian oscillator, indicating that these rhythms are ultimately downstream of the conventional circadian clock. Typically, they are involved in cellular responses to stress, suggesting that ultradian transcriptional rhythms respond to twice daily stresses.

System-driven circadian oscillations

Fig. 2: Hughes et al. (2012b)
~100 genes oscillate in the mouse liver, despite ablation of the local, peripheral clock.

Rhythms of snoRNA host genes

Fig. 3: Hughes et al. (2012a)
Non-coding, snoRNA host genes oscillate in the fly brain

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Hughes Lab
Department of Biology
University of Missouri, St. Louis
(Starting in August, 2013)