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Physiol. Genomics (June 5, 2007). doi:10.1152/physiolgenomics.00066.2007
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Submitted on March 21, 2007
Accepted on May 30, 2007

Identification of the Circadian Transcriptome in Adult Mouse Skeletal Muscle

John J. McCarthy1, Jessica L Andrews2, Erin L. McDearmon3, Kenneth S Campbell4, Brigham K. Barber1, Brooke H. Miller5, John R. Walker6, John B. Hogenesch7, Joseph S. Takahashi8, and Karyn A Esser1*

1 Physiology, Kentucky, Lexington, Kentucky, United States
2 Kinesiology, University of Illinois, Chicago, Chicago, Illinois, United States; Muscolskeletal, MC7R2, Eli Lilly, Indianapolis, Indiana, United States
3 Howard Hughes Medical Institute, Evanston, Illinois, United States; Neurobiology & Physiology, Northwestern University, Evanston, Illinois, United States
4 Department of Physiology, University of Kentucky, Lexington, Kentucky, United States
5 Scripps, Jupiter, Florida, United States
6 The Genomics Institute of the Novartis Research Foundation, San Diego, California, United States
7 The Genomics Institute of the Novartis Research Foundation, San Diego, California, United States; Institute for Translational Medicine and Therapeutics, University of Pennsylvania School of Medicine, Philadelphia , Pennsylvania, United States
8 Howard Hughes Medical Institute, United States; Neurobiology & Physiology, Northwestern University, Evanston, Illinois, United States

* To whom correspondence should be addressed. E-mail: kaesse2{at}uky.edu.

Circadian rhythms are approximate 24-hr behavioral and physiological cycles that function to prepare an organism for daily environmental changes. The basic clock mechanism is a network of transcriptional-translational feedback loops that drive rhythmic expression of genes over a 24-hr period. The objectives of this study were to identify transcripts with a circadian pattern of expression in adult skeletal muscle and to determine the effect of the Clock mutation on gene expression. Expression profiling on muscle samples collected every 4 hours for 48 hours was performed. Using COSOPT, a total of 215 transcripts were identified as having a circadian pattern of expression. Real time PCR results verified the circadian expression of the core clock genes, Bmal1, Per2 and Cry2. Annotation revealed cycling genes were involved in a range of biological processes including transcription, lipid metabolism, protein degradation, ion transport and vesicular trafficking. The tissue specificity of the skeletal muscle circadian transcriptome was highlighted by the presence of known muscle-specific genes such as Myod1, Ucp3, Atrogin1 (Fbxo32) and Myh1 (myosin heavy chain IIX). Expression profiling was also performed on muscle from the Clock mutant mouse and sarcomeric genes such as actin, titin and many mitochondrial genes were significantly down-regulated in the muscle of Clock mutant mice. Defining the circadian transcriptome in adult skeletal muscle and identifying the significant alterations in gene expression that occur in muscle of the Clock mutant mouse provides the basis for understanding the role of circadian rhythms in the daily maintenance of skeletal muscle.




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