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.
Highlights
Biological rhythms are widespread in behavior and physiology [1], and in past decades, the principal molecular mechanisms driving 24-h rhythms at the cellular level have been identified [2]
We know considerably less about ultradian rhythmicity, which is a catch-all term for biological rhythms, with periods ranging from milliseconds to hours
Of the 323 probes that were identified as ultradian probes in the original publication [14], our method confirmed ultradian expression patterns in 175, exposing a large overlap between both methods, which adds to the validation of our analysis method
Summary
Biological rhythms are widespread in behavior and physiology [1], and in past decades, the principal molecular mechanisms driving 24-h rhythms at the cellular level have been identified [2]. Well-known examples of such rhythms include cycles in behavioral arousal [6,7,8,9], glucocorticoid level [10], rapid eye movement (REM)–non-REM sleep cycle [11], central monoamine release [12], cellular metabolism [13], and gene expression [14]. ABBREVIATIONS: KEGG, Kyoto Encyclopedia of Genes and Genomes; NIH, U.S National Institutes of Health; REM, rapid eye movement Ultradian rhythms in in vitro cell cultures have been reported for glucocorticoid release [17, 18], single-cell firing [19], and protein synthesis [20] suggesting that these rhythms are intrinsically driven at the cellular level, but mechanisms driving them remain unknown. One of the main reasons for this lack of success may be that ultradian rhythms are often coexpressed with circadian rhythms, which results in ultradian rhythms being overshadowed, or masked by the coexpressed circadian rhythms and their harmonics
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
