Pathway-level analysis of genome-wide circadian dynamics in diverse tissues in rat and mouse

Acevedo, Alison; Mavroudis, Panteleimon D.; DuBois, Debra C.; Almon, Richard R.; Jusko, William J.; Androulakis, Ioannis P.

doi:10.1007/s10928-021-09750-3

Cited by 3 publications

(2 citation statements)

References 77 publications

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“…In some studies, the structure of the pathway, i.e. whether certain pathway components have opposing roles, is also taken into account (Acevedo et al, 2021; Zhang et al, 2014). However, evaluating the overrepresentation of pathway components among the rhythmic genes can still be misleading, since the circadian control of just a few rate-limiting steps might be sufficient to induce rhythms in a pathway function (Fustin et al, 2012; Kim and Reed, 2021; Panda et al, 2002).…”

Section: Introductionmentioning

confidence: 99%

Gene expression signatures predict circadian rhythms in oncogenic pathways

Winkler

Ananthasubramaniam

Herzel

2022

Preprint

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Day-night environmental cycles together with our own adaptive rhythms in behavior and physiology lead to rhythmicity of various processes on the cellular level, including cell signaling. Despite many implications of such daily changes in signaling, the quantification of such rhythms and estimates of peak phases of pathway activities in various tissues are missing. Governed mainly by posttranslational modifications, a pathway activity might not be well quantified via the expression level of pathway components. Instead, a gene expression signatures approach can be used to score activity of various pathways. Here, we apply such gene expression signatures on circadian time series transcriptomics data to infer rhythmicity in cellular signaling. We show that, across multiple datasets, the gene expression signatures predict the presence of rhythmicity in EGFR, PI3K and p53 pathways in mouse liver. With the focus on EGFR pathway, we pinpoint the most influential signature genes for the overall rhythmicity in the activity scores for this pathway. These findings suggest that time of the day is an important factor to consider in studies on signaling. Simultaneously, this study provides a new paradigm to use circadian transcriptomics to get at temporal dynamics of pathway activation.

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Section: Introductionmentioning

confidence: 99%

Gene expression signatures predict circadian rhythms in oncogenic pathways

Winkler

Ananthasubramaniam

Herzel

2022

Preprint

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“…Circadian regulation is astonishingly widespread: nearly half of all mammalian genes are rhythmically expressed in one or more tissues (Yan et al, 2008; Acevedo et al, 2021). Besides the SCN neurons, clock genes and proteins have been observed in cells and tissues throughout the body (such as the lung, liver, skeletal muscle, and heart), indicating the existence of endogenous clocks among the peripheral cells (Welsh et al, 2004; Yoo et al, 2004; Zhang et al, 2014).…”

Section: Introductionmentioning

confidence: 99%

The SCN-HPA-Periphery Circadian Timing System: Mathematical Modeling of Clock Synchronization and the Effects of Photoperiod on Jetlag Adaptation

Androulakis

2023

J Biol Rhythms

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Synchronizing the circadian timing system (CTS) to external light/dark cycles is crucial for homeostasis maintenance and environmental adaptation. The CTS is organized hierarchically, with the central pacemaker located in the suprachiasmatic nuclei (SCN) generating coherent oscillations that are entrained to light/dark cycles. These oscillations regulate the release of glucocorticoids by the hypothalamus-pituitary-adrenal (HPA) axis, which acts as a systemic entrainer of peripheral clocks throughout the body. The SCN adjusts its network plasticity in response to variations in photoperiod, leading to changes in the rhythmic release of glucocorticoids and ultimately impacting peripheral clocks. However, the effects of photoperiod-induced variations of glucocorticoids on the synchronization of peripheral clocks are not fully understood, and the interaction between jetlag adaption and photoperiod changes is unclear. This study presents a semi-mechanistic mathematical model to investigate how the CTS responds to changes in photoperiod. Specifically, the study focuses on the entrainment properties of a system composed of the SCN, HPA axis, and peripheral clocks. The results show that high-amplitude glucocorticoid rhythms lead to a more coherent phase distribution in the periphery. In addition, our study investigates the effect of photoperiod exposure on jetlag recovery time and phase shift, proposing different interventional strategies for eastward and westward jetlag. The findings suggest that decreasing photic exposure before jetlag during eastward traveling and after jetlag during westward traveling can accelerate jetlag readaptation. The study provides insights into the mechanisms of CTS organization and potential recovery strategies for transitions between time zones and lighting zones.

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