TRANSCRIPTOME 2002: From Functional Genomics to Systems
Definition of the Transcriptional and Translational Response to a Physiological Stimulus: A Cross-Species Time Series Muscle Study in Human Volunteers and Rats
Yi-Wen Chen1, Eric P Hoffman1, Gustavo Nader2, Keith R. Baar2, Karyn A. Esser2, Monica J. Hubal3, Paul D. Thompson4, Priscilla M. Clarkson3, 1Children’s National Medical Center, Washington, DC; 2University of Illinois, Chicago, IL; 3University of Massachusetts, Amherst, MA; 4Hartford Hospital, Hartford, CT
Muscle is a highly adaptable tissue specifically responds to change in the amount and type of activity. Here, we compare transcriptional cascades resulting from a single bout of muscle activity, in both human volunteers and an experimental rat model system. Expression profiling was done on human or grouped rat time series muscle samples, using Human U95Av2 microarrays (~12,000 genes), and rat U34A (~8,000 genes/ESTs). Six human arrays from three volunteers, and 48 rat arrays were done. Human data were analyzed to detect consistent intra-patient expression changes. Both rat total and polyribosomal RNAs at two different time points were studied to investigate transcriptional and translational regulations. In the human study, 34 genes were differentially regulated in common among three subjects (exercised vs. control). Of these 34, 24 were on the rat arrays, and half (11) showed similar dysregulation in the rat model. Most genes were involved in cell growth regulation and stress response pathways. About 10% of the differentially regulated genes in the rat showed regulation that was primarily translational. Muscle is post-mitotic, and must show cell growth without activation of mitotic pathways in myofibers. The expression profiles show evidence of this balance in growth promoting and growth inhibiting gene regulation.
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