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Transcriptomic analyses reveal rhythmic and CLOCK-driven pathways in human skeletal muscle

Perrin, Laurent; Loizides-Mangold, Ursula; Chanon, Stephanie; Gobet, Cedric; Hulo, Nicolas; Isenegger, Laura; Weger, Benjamin D .; Migliavacca, Eugenia; Charpagne, Aline; Betts, James A.; Walhin, Jean-Philippe; Templeman, Iain; Stokes, Keith; Thompson, Dylan; Tsintzas, Kostas; Robert, Maud; Howald, Cedric; Riezman, Howard; Feige, Jerome N.; Karagounis, Leonidas G.; Johnston, Jonathan D.; Dermitzakis, Emmanouil T.; Gachon, Frederic; Lefai, Etienne; Dibner, Charna

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Laurent Perrin

Ursula Loizides-Mangold

Stephanie Chanon

Cedric Gobet

Nicolas Hulo

Laura Isenegger

Benjamin D . Weger

Eugenia Migliavacca

Aline Charpagne

James A. Betts

Jean-Philippe Walhin

Iain Templeman

Keith Stokes

Dylan Thompson

Professor of Human Physiology

Maud Robert

Cedric Howald

Howard Riezman

Jerome N. Feige

Leonidas G. Karagounis

Jonathan D. Johnston

Emmanouil T. Dermitzakis

Frederic Gachon

Etienne Lefai

Charna Dibner


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.


Perrin, L., Loizides-Mangold, U., Chanon, S., Gobet, C., Hulo, N., Isenegger, L., …Dibner, C. (2018). Transcriptomic analyses reveal rhythmic and CLOCK-driven pathways in human skeletal muscle. eLife, 7, Article e34114.

Journal Article Type Article
Acceptance Date Apr 4, 2018
Online Publication Date Apr 16, 2018
Publication Date Apr 16, 2018
Deposit Date Nov 19, 2018
Publicly Available Date Nov 19, 2018
Electronic ISSN 2050-084X
Publisher eLife Sciences Publications
Peer Reviewed Peer Reviewed
Volume 7
Article Number e34114
Public URL
Publisher URL
Contract Date Nov 19, 2018


Transcriptomic analyses reveal rhythmic and CLOCK-driven pathways (4.3 Mb)

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