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Thyroid hormone receptor coactivators and corepressors

R J Koenig1

  • 1Division of Endocrinology, University of Michigan Medical Center, Ann Arbor 48109-0678, USA.

Thyroid : Official Journal of the American Thyroid Association
|September 16, 1998
PubMed
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Thyroid hormone receptors (TRs) regulate gene transcription by interacting with corepressors or coactivators. Triiodothyronine (T3) binding to TRs shifts this interaction, activating gene expression through chromatin remodeling.

Area of Science:

  • Molecular Biology
  • Endocrinology
  • Genetics

Background:

  • Thyroid hormone receptors (TRs) bind DNA and regulate gene transcription.
  • TRs interact with nuclear proteins to modulate gene expression.
  • Gene regulation by TRs is dependent on the presence or absence of triiodothyronine (T3).

Purpose of the Study:

  • To elucidate the molecular mechanisms by which TRs regulate gene transcription.
  • To understand the role of corepressors and coactivators in T3-mediated gene regulation.
  • To detail the process of gene activation by T3.

Main Methods:

  • Analysis of protein-DNA interactions.
  • Investigation of protein-protein interactions.
  • Study of chromatin remodeling via histone acetylation and deacetylation.

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Main Results:

  • Unliganded TRs recruit corepressors, leading to histone deacetylation and gene repression.
  • T3 binding induces a conformational change in TRs, releasing corepressors and recruiting coactivators.
  • Coactivators facilitate gene activation through histone acetylation and other mechanisms.

Conclusions:

  • T3-mediated gene activation involves a two-step process: removal of repression and induction of transcription.
  • TRs act as molecular switches, integrating signals from T3 to control gene expression.
  • Chromatin modification is a key mechanism in thyroid hormone-regulated gene transcription.