Harmonics of Circadian Gene Transcription in Mammals

By Michael Hughes, Luciano DiTacchio, K. R. Hayes, Christopher Vollmers, S. Pulivarthy, J. Baggs, Satchidananda Panda, John B. Hogenesch. PLoS Genetics, 2009

689 citations recorded by the source corpus.

The circadian clock is a molecular and cellular oscillator found in most mammalian tissues that regulates rhythmic physiology and behavior. Numerous investigations have addressed the contribution of circadian rhythmicity to cellular, organ, and organismal physiology. We recently developed a method to look at transcriptional oscillations with unprecedented precision and accuracy using high-density time sampling. Here, we report a comparison of oscillating transcription from mouse liver, NIH3T3, and U2OS cells. Several surprising observations resulted from this study, including a 100-fold difference in the number of cycling transcripts in autonomous cellular models of the oscillator versus tissues harvested from intact mice. Strikingly, we found two clusters of genes that cycle at the second and third harmonic of circadian rhythmicity in liver, but not cultured cells. Validation experiments show that 12-hour oscillatory transcripts occur in several other peripheral tissues as well including heart, kidney, and lungs. These harmonics are lost ex vivo, as well as under restricted feeding conditions. Taken in sum, these studies illustrate the importance of time sampling with respect to multiple testing, suggest caution in use of autonomous cellular models to study clock output, and demonstrate the existence of harmonics of circadian gene expression in the mouse.

Subfields: Aging, Endocrine and Autonomic Systems, Plant Science

View Paper: https://www.semanticscholar.org/paper/220fd3f7b71bc9bd2a48a3329fc594e11d73d600

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Citations in the corpus

Time restricted feeding without reducing caloric intake prevents metabolic diseases in mice fed a high fat diet (2012, neutral): “Several genes encoding enzymes of purine and pyrimidine biosynthesis and nucleotide salvage pathways are the direct targets of the circadian activator BMAL1 (Uridine monophosphate synthase [Umps] and Thymidine kinase 1 [Tk1]) and/or exhibit rhythmic expression patterns (phosphoribosylpyrophosphate s”
A circadian gene expression atlas in mammals: Implications for biology and medicine (2014, methodology): “Mice were prepared as previously described (8).”
Molecular Architecture of the Mammalian Circadian Clock (2013, background): “Importantly, the interaction of systemically controlled genes with the molecular machinery of peripheral clocks helps to give rise to tissue-specific patterns and 12-hour harmonics of circadian gene expression, driven by the integration of transcriptional and post-transcriptional mechanisms (Figure ”
JTK_CYCLE: an efficient non-parametric algorithm for detecting rhythmic components in genome-scale datasets (2010, methodology): “COSOPT and Fisher’s G tests were performed on these data as previously described (Hughes et al., 2009).”
The mammalian circadian timing system: organization and coordination of central and peripheral clocks. (2010, background): “Since then, circadian gene expression has been observed in a variety of cultured cell lines and primary fibroblasts, including murine NIH-3T3 fibroblasts (208), mouse and human primary fibroblasts (209), and human U2OS osteosarkoma cells (193).”
CENTRAL AND PERIPHERAL CIRCADIAN CLOCKS IN MAMMALS (2012, background): “These endogenous cellular clocks drive extensive rhythms of gene transcription, with 3–10% of all mRNAs in a given tissue showing circadian rhythms in steadystate levels (Akhtar et al. 2002, Duffield et al. 2002, Hughes et al. 2009, Miller et al. 2007, Panda et al. 2002, Storch et al. 2002).”
Reprogramming of the Circadian Clock by Nutritional Challenge (2013, neutral): “Conversely, metabolic disruptions such as the restriction of energy intake to a phase that opposes that of the traditional feeding phase, can reset some peripheral clocks almost entirely, disrupting energy balance (Arble et al., 2009; Damiola et al., 2000; Hughes et al., 2009; Stokkan et al., 2001; ”
Time of feeding and the intrinsic circadian clock drive rhythms in hepatic gene expression (2009, background): “This largely surpasses the combined numbers of food-only (617 transcripts are rhythmic in cry1 / ;cry2 / mice under tRF conditions) and circadian clockonly (368 rhythmic transcripts under fasting condition in WT mice) driven transcripts, even when lower sampling frequency is taken into account (26).”