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Transcriptomic analyses reveal rhythmic and CLOCK-driven pathways in human skeletal muscle
Perrin, Laurent Loizides-Mangold, Ursula Chanon, Stéphanie Gobet, Cédric Hulo, Nicolas Isenegger, Laura Weger, Benjamin D. Migliavacca, Eugenia Charpagne, Aline Betts, James A.
Perrin, Laurent
Loizides-Mangold, Ursula
Chanon, Stéphanie
Gobet, Cédric
Hulo, Nicolas
Isenegger, Laura
Weger, Benjamin D.
Migliavacca, Eugenia
Charpagne, Aline
Betts, James A.
Author
Perrin, Laurent
Loizides-Mangold, Ursula
Chanon, Stéphanie
Gobet, Cédric
Hulo, Nicolas
Isenegger, Laura
Weger, Benjamin D.
Migliavacca, Eugenia
Charpagne, Aline
Betts, James A.
Walhin, Jean-Philippe
Templeman, Iain
Stokes, Keith A.
Karagounis, Leonidas
Thompson, Dylan
Tsintzas, Kostas
Robert, Maud
Howald, Cedric
Riezman, Howard
Feige, Jerome N.
Johnston, Jonathan D.
Dermitzakis, Emmanouil T.
Gachon, Frédéric
Lefai, Etienne
Dibner, Charna
Loizides-Mangold, Ursula
Chanon, Stéphanie
Gobet, Cédric
Hulo, Nicolas
Isenegger, Laura
Weger, Benjamin D.
Migliavacca, Eugenia
Charpagne, Aline
Betts, James A.
Walhin, Jean-Philippe
Templeman, Iain
Stokes, Keith A.
Karagounis, Leonidas
Thompson, Dylan
Tsintzas, Kostas
Robert, Maud
Howald, Cedric
Riezman, Howard
Feige, Jerome N.
Johnston, Jonathan D.
Dermitzakis, Emmanouil T.
Gachon, Frédéric
Lefai, Etienne
Dibner, Charna
Abstract
Circadian regulation of transcriptional processes has a broad impact on cell metabolism. Here, we compared the diurnal transcriptome of human skeletal muscle conducted on serial muscle biopsies in vivo with profiles of human skeletal myotubes synchronized in vitro. More extensive rhythmic transcription was observed in human skeletal muscle compared to in vitro cell culture as a large part of the in vivo mRNA rhythmicity was lost in vitro. siRNA-mediated clock disruption in primary myotubes significantly affected the expression of ~8% of all genes, with impact on glucose homeostasis and lipid metabolism. Genes involved in GLUT4 expression, translocation and recycling were negatively affected, whereas lipid metabolic genes were altered to promote activation of lipid utilization. Moreover, basal and insulin-stimulated glucose uptake were significantly reduced upon CLOCK depletion. Our findings suggest an essential role for the circadian coordination of skeletal muscle glucose homeostasis and lipid metabolism in humans.
Keywords
circadian rgulation, rhythmic transcription, CLOCK, glucose, cell biology, circadian oscillators, human skeletal muscle, RNA sequencing
Date
2018
Type
Journal article
Journal
Book
Volume
7
Issue
Page Range
1-30
Article Number
ACU Department
Mary MacKillop Institute for Health Research
Faculty of Health Sciences
Faculty of Health Sciences
Collections
Relation URI
Source URL
Event URL
Open Access Status
Open access
License
CC BY 4.0
File Access
Open
Notes
© 2018, Perrin et al.
This article is distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use and redistribution provided that the original author and source are credited.
Funding: This work was funded by the Sinergia Swiss National Science Foundation (Grant No. CRSII3-154405 to HR, CD, EL), the Swiss National Science Foundation (Grant No. 31003A-166700 (CD), the Fondation Privée de HUG, Fondation Ernst et Lucie Schmidheiny, the Société Académique de Genève (CD) and by the United Kingdom Biotechnology and Biological Sciences Research Council Grant BB/I008470/1 (JDJ).
This article is distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use and redistribution provided that the original author and source are credited.
Funding: This work was funded by the Sinergia Swiss National Science Foundation (Grant No. CRSII3-154405 to HR, CD, EL), the Swiss National Science Foundation (Grant No. 31003A-166700 (CD), the Fondation Privée de HUG, Fondation Ernst et Lucie Schmidheiny, the Société Académique de Genève (CD) and by the United Kingdom Biotechnology and Biological Sciences Research Council Grant BB/I008470/1 (JDJ).