In Vivo Regulation of Human Skeletal Muscle Gene Expression by Thyroid Hormone
- Karine Clément1,6,
- Nathalie Viguerie2,
- Maximilian Diehn3,
- Ash Alizadeh3,
- Pierre Barbe2,
- Claire Thalamas4,
- John D. Storey5,
- Patrick O. Brown3,
- Greg S. Barsh1,7, and
- Dominique Langin2,7
- 1Department of Pediatrics and Genetics, Howard Hughes Medical Institute, Beckman Center, Stanford University School of Medicine, Stanford, California 94305, USA; 2Institut National de la Santé et de la Recherche Médicale Unit 317, Louis Bugnard Institute, Paul Sabatier University, Rangueil Hospital, 31403 Toulouse, France; 3Department of Biochemistry, Howard Hughes Medical Institute, Beckman Center, Stanford University School of Medicine, Stanford, California 94305, USA; 4Clinical Investigation Center, Purpan Hospital, Pavillon Riser, 31059 Toulouse, France; 5Department of Statistics, Stanford University, Stanford, California 94305, USA
Abstract
Thyroid hormones are key regulators of metabolism that modulate transcription via nuclear receptors. Hyperthyroidism is associated with increased metabolic rate, protein breakdown, and weight loss. Although the molecular actions of thyroid hormones have been studied thoroughly, their pleiotropic effects are mediated by complex changes in expression of an unknown number of target genes. Here, we measured patterns of skeletal muscle gene expression in five healthy men treated for 14 days with 75 μg of triiodothyronine, using 24,000 cDNA element microarrays. To analyze the data, we used a new statistical method that identifies significant changes in expression and estimates the false discovery rate. The 381 up-regulated genes were involved in a wide range of cellular functions including transcriptional control, mRNA maturation, protein turnover, signal transduction, cellular trafficking, and energy metabolism. Only two genes were down-regulated. Most of the genes are novel targets of thyroid hormone. Cluster analysis of triiodothyronine-regulated gene expression among 19 different human tissues or cell lines revealed sets of coregulated genes that serve similar biologic functions. These results define molecular signatures that help to understand the physiology and pathophysiology of thyroid hormone action.
[The list of transcripts corresponding to up-regulated and down-regulated genes is available as a web supplement at http://www.genome.org.]
Footnotes
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↵6 Present address: Laboratoire et Service de Médecine et Nutrition, EA Université Paris 6, Hôtel-Dieu, Place du Parvis Notre-Dame 75004 Paris, France.
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↵7 Corresponding authors.
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E-MAIL langin{at}toulouse.inserm.fr; FAX (33)-5-62172950.
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E-MAIL gbarsh{at}cmgm.stanford.edu; FAX (650) 723-1399.
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Article and publication are at http://www.genome.org/cgi/doi/10.1101/gr.207702.
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- Received July 26, 2001.
- Accepted November 30, 2001.
- Cold Spring Harbor Laboratory Press
