Compensation for intracellular environment in expression levels of mammalian circadian clock genes

Ritsuko Matsumura,Koichi Node,Akihiko Okamoto,Makoto Akashi

doi:10.1038/srep04032

Ritsuko Matsumura, Koichi Node + Show 2 more

Open Access

https://doi.org/10.1038/srep04032

Copy DOI

Journal: Scientific Reports	Publication Date: Feb 7, 2014
Citations: 26	License type: CC BY 3.0

Affiliation: Yamaguchi University, Saga University

Abstract

The circadian clock is driven by transcriptional oscillation of clock genes in almost all body cells. To investigate the effect of cell type-specific intracellular environment on the circadian machinery, we examined gene expression profiles in five peripheral tissues. As expected, the phase relationship between expression rhythms of nine clock genes was similar in all tissues examined. We also compared relative expression levels of clock genes among tissues, and unexpectedly found that quantitative variation remained within an approximately three-fold range, which was substantially smaller than that of metabolic housekeeping genes. Interestingly, circadian gene expression was little affected even when fibroblasts were cultured with different concentrations of serum. Together, these findings support a hypothesis that expression levels of clock genes are quantitatively compensated for the intracellular environment, such as redox potential and metabolite composition. However, more comprehensive studies are required to reach definitive conclusions.

Highlights

The circadian clock is driven by transcriptional oscillation of clock genes in almost all body cells
While gene expression profiles, metabolite composition, and redox potential vary depending on cell type, and the intracellular environment shows wide variation in a cell type-specific manner, it remains unclear how the core clock machinery is maintained against the variable intracellular environment
We found that the phase differences among these peripheral clocks were within approximately 2 hours, indicating that the phase of peripheral circadian clocks are somewhat tissue-specific but synchronized within a similar range in vivo

Summary

Introduction

The circadian clock is driven by transcriptional oscillation of clock genes in almost all body cells. To investigate the effect of cell type-specific intracellular environment on the circadian machinery, we examined gene expression profiles in five peripheral tissues. Circadian gene expression was little affected even when fibroblasts were cultured with different concentrations of serum. Together, these findings support a hypothesis that expression levels of clock genes are quantitatively compensated for the intracellular environment, such as redox potential and metabolite composition. Expression of the Period (Per) genes is driven by the CLOCK (NPAS2)/BMAL1 transcription complex. To better understand the maintenance and control of the core clock machinery across different intracellular environments, we compared the temporal expression pattern of clock genes among a range of peripheral tissues. We examined the change in circadian gene expression in response to different nutritional conditions

Methods

Results

Conclusion