In Vivo Regulation of Human Skeletal Muscle Gene Expression by Thyroid Hormone

Overview

Journal Genome Res

Specialty Genetics

Date 2002 Feb 6

PMID 11827947

Citations 51

Authors

Karine Clement

Nathalie Viguerie

Maximilian Diehn

Ash Alizadeh

Pierre Barbe

Claire Thalamas

John D Storey

Patrick O Brown

Greg S Barsh

Dominique Langin

Affiliations

Soon will be listed here.

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 microg 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.

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