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Related Experiment Videos

Characteristics of a negative thyroid hormone response element

F E Carr1, N C Wong

  • 1Kyle Metabolic Unit Research Laboratories, Department of Clinical Investigation, Walter Reed Army Medical Center, Washington DC 20307.

The Journal of Biological Chemistry
|February 11, 1994
PubMed
Summary

Thyroid hormone L-triiodothyronine (T3) represses rat thyrotropin beta-subunit gene transcription via a negative thyroid hormone response element (nT3RE). This nT3RE unexpectedly resembles a TREpal half-site, crucial for T3-mediated gene repression.

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Area of Science:

  • Molecular Endocrinology
  • Gene Regulation
  • Thyroid Hormone Action

Background:

  • Thyroid hormones regulate gene transcription, either stimulating or repressing it.
  • While positive regulation involves TREpal, the negative response element (nT3RE) for thyroid hormone action is not well-defined.

Purpose of the Study:

  • To identify and characterize the DNA sequences mediating thyroid hormone's inhibitory effects on rat thyrotropin beta-subunit (rTSH beta) gene transcription.
  • To elucidate the role of thyroid hormone receptors (T3R) in this negative regulation.

Main Methods:

  • Transient expression assays in GH3 pituitary tumor cells using plasmid constructs with putative nT3RE sequences.
  • Testing of a half-site motif construct and cotransfection studies in T3R-deficient cells.

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Main Results:

  • The putative nT3RE from rTSH beta mediated negative regulation by L-triiodothyronine (T3).
  • A construct with a TREpal half-site motif also showed decreased activity in response to T3.
  • Both alpha and beta isoforms of T3R were required for T3's inhibitory effects, and both bind to the nT3RE and half-site motif.

Conclusions:

  • The repressive effects of T3 on rTSH beta gene transcription are mediated by a specific nT3RE.
  • This nT3RE shares characteristics with a TREpal half-site, suggesting a dual role for such motifs in thyroid hormone-mediated gene regulation.