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Related Experiment Videos

Novel location and function of a thyroid hormone response element

J Bigler1, R N Eisenman

  • 1Division of Basic Sciences, Fred Hutchinson Cancer Research Center, Seattle, WA 98104, USA.

The EMBO Journal
|November 15, 1995
PubMed
Summary

Researchers identified a novel thyroid hormone response element (TRE) in clone 144 that regulates gene expression. This TRE, located in the 3' untranslated region, is activated by the thyroid hormone receptor (TR) in the absence of thyroid hormone (T3).

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Area of Science:

  • Molecular Biology
  • Endocrinology
  • Genetics

Background:

  • Thyroid hormone receptors (TRs) regulate gene expression through thyroid hormone response elements (TREs).
  • TREs are typically found in promoter regions, influencing gene transcription.
  • The role of TREs in 3' untranslated regions (UTRs) remains less understood.

Purpose of the Study:

  • To identify and characterize novel TRE-containing sequences involved in thyroid hormone regulation.
  • To investigate the function and location of a newly identified TRE (clone 144) within cellular mRNAs.
  • To elucidate the mechanism of TR-mediated gene regulation by a 3' UTR TRE.

Main Methods:

  • Immunoprecipitation of nuclear TR-DNA complexes from GH4 rat pituitary tumor cells.
  • Hybridization analysis of mRNAs using a TRE-containing genomic clone (clone 144).

Related Experiment Videos

  • Reporter construct assays in 293 cells to assess TR regulation of the clone 144 TRE.
  • DNase I protection assays to map the TRE sequence.
  • Deletion analysis of flanking sequences in the reporter construct.

    • Main Results:

    • A novel TRE-containing sequence (clone 144) was identified and associated with specific mRNAs.
    • These mRNAs are transcriptionally upregulated in the absence of thyroid hormone (T3) and repressed in its presence.
    • The clone 144 TRE, located in the 3' UTR, conferred TR-dependent regulation in reporter assays.
    • Regulation occurred when the TRE was in the 3' UTR, but not upstream of the promoter.
    • Flanking sequences of the clone 144 TRE were essential for TR-mediated regulation.

    Conclusions:

    • A novel TRE in the 3' UTR of specific mRNAs is regulated by TR.
    • TR-mediated regulation via a 3' UTR TRE differs mechanistically from promoter-proximal TREs.
    • This finding expands the understanding of thyroid hormone's regulatory mechanisms in gene expression.