Activation of the thyroid hormone receptor alpha gene promoter by the orphan nuclear receptor ERR alpha

Oncogene. 1998 Nov 12;17(19):2429-35. doi: 10.1038/sj.onc.1202167.


The superfamily of nuclear receptors comprises transcription factors that depend on a ligand for their activity. In addition, the superfamily includes a number of orphan receptors, for which no ligand is known. We report here that the orphan receptor estrogen receptor related alpha receptor (ERR alpha) stimulates the expression of the thyroid hormone receptor alpha (TR alpha) gene promoter. We characterized a responsive site that is both necessary and sufficient for ERR alpha-induced transactivation. In addition, we show that both TR alpha and ERR alpha are coexpressed in embryonic intestine, brown fat and heart as well as in the adult gonads. In the testis, expression of both receptors can be found in the seminiferous tubes where it is totally restricted to spermatocytes I. Altogether this suggests that TR alpha is an in vivo target of ERR alpha.

Publication types

  • Comparative Study

MeSH terms

  • Adipose Tissue, Brown / embryology
  • Adipose Tissue, Brown / growth & development
  • Adipose Tissue, Brown / metabolism
  • Animals
  • Base Sequence
  • Cell Line
  • Consensus Sequence
  • Female
  • Fetal Heart / metabolism
  • Fibroblasts
  • Gene Expression Regulation, Developmental*
  • Genes, Reporter
  • Gonads / embryology
  • Gonads / growth & development
  • Gonads / metabolism
  • HeLa Cells
  • Humans
  • Intestinal Mucosa / metabolism
  • Intestines / embryology
  • Luciferases / biosynthesis
  • Male
  • Mice
  • Molecular Sequence Data
  • Myocardium / metabolism
  • Organ Specificity
  • Promoter Regions, Genetic*
  • Rats
  • Receptors, Cytoplasmic and Nuclear / biosynthesis
  • Receptors, Cytoplasmic and Nuclear / genetics
  • Receptors, Cytoplasmic and Nuclear / physiology*
  • Receptors, Estrogen / biosynthesis
  • Receptors, Estrogen / genetics
  • Receptors, Estrogen / physiology*
  • Receptors, Thyroid Hormone / biosynthesis
  • Receptors, Thyroid Hormone / genetics*
  • Recombinant Fusion Proteins / biosynthesis
  • Regulatory Sequences, Nucleic Acid
  • Sequence Alignment
  • Sequence Homology, Nucleic Acid
  • Species Specificity
  • Transcriptional Activation*


  • ERRalpha estrogen-related receptor
  • Receptors, Cytoplasmic and Nuclear
  • Receptors, Estrogen
  • Receptors, Thyroid Hormone
  • Recombinant Fusion Proteins
  • Luciferases