RT Journal
A1 Clément, Karine
A1 Viguerie, Nathalie
A1 Diehn, Maximilian
A1 Alizadeh, Ash
A1 Barbe, Pierre
A1 Thalamas, Claire
A1 Storey, John D.
A1 Brown, Patrick O.
A1 Barsh, Greg S.
A1 Langin, Dominique
T1 In Vivo Regulation of Human Skeletal Muscle Gene Expression by Thyroid Hormone
JF Genome Research 
JO Genome Research 
YR 2002 
FD February 01 
VO 12 
IS 2 
SP 281 
OP 291 
DO 10.1101/gr.207702 
UL http://genome.cshlp.org/content/12/2/281.abstract 
AB 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.]