Unmasking ultradian rhythms in gene expression

Abstract

Biological oscillations with an ultradian time scale of 1 to several hours include cycles in behavioral arousal, episodic glucocorticoid release, and gene expression. Ultradian rhythms are thought to have an extrinsic origin because of a perceived absence of ultradian rhythmicity in vitro and a lack of known molecular ultradian oscillators. We designed a novel, non–spectral-analysis method of separating ultradian from circadian components and applied it to a published gene expression dataset with an ultradian sampling resolution. Ultradian rhythms in mouse hepatocytes in vivo have been published, and we validated our approach using this control by confirming 175 of 323 ultradian genes identified in a prior study and found 862 additional ultradian genes. For the first time, we now report ultradian expression of >900 genes in vitro. Sixty genes exhibited ultradian transcriptional rhythmicity, both in vivo and in vitro, including 5 genes involved in the cell cycle. Within these 60 genes, we identified significant enrichment of specific DNA motifs in the 1000 bp proximal promotor, some of which associate with known transcriptional factors. These findings are in strong support of instrinsically driven ultradian rhythms and expose potential molecular mechanisms and functions underlying ultradian rhythms that remain unknown.—Van der Veen, D. R., Gerkema, M. P. Unmasking ultradian rhythms in gene expression.

Systematic Analysis of Mouse Genome Reveals Distinct Evolutionary and Functional Properties Among Circadian and Ultradian Genes

“…Our reference mouse gene lists were taken from a single publicly available data set ( Hughes et al, 2009 ). Different valuable although not fully comparable methodological approaches have been recently used in order to detect circadian and ultradian signals within transcriptomes (e.g., van der Veen and Gerkema, 2017 ; Zhu et al, 2017 ). The results of our well-established bioinformatics approach partly overlap with ultradian gene sets identified by these studies, which use different criteria to identify harmonics of circadian rhythmicity in gene expression.…”

Systematic analysis of mouse genome reveals distinct evolutionary and functional properties among circadian and ultradian genes

“…Our reference mouse gene lists were taken from a single publicly available data set (Hughes 2009 PMID: 19343201 ). Different valuable although not fully comparable methodological approaches have been recently used in order to detect circadian and ultradian signals within transcriptomes (e.g., Zhu 2017 28591634 ; Van der Veen 2017 27871062 ). The results of our well-established bioinformatics approach partly overlap with ultradian gene sets identified by these studies, which define different criteria to identify harmonics of circadian rhythmicity in gene expression.…”

Guidelines for Genome-Scale Analysis of Biological Rhythms

“…We note that Haystack ( Mockler et al, 2007 ) and ZeitZeiger ( Hughey et al, 2016 ) are less sensitive to waveform shape than other algorithms. Some approaches are optimized for distinguishing ultradian rhythms from conventional 24-h rhythms ( van der Veen and Gerkema, 2017 ). In many cases, however, investigators will have the greatest statistical power when searching for rhythms equal to conventional 24-h cycles.…”