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Thyroid hormone-mediated negative transcriptional regulation of Necdin expression

Maria Nygård1, Nathalie Becker, Barbara Demeneix

  • 1Department of Biosciences at Novum, Karolinska Institutet, 141 57 Huddinge, Sweden.

Journal of Molecular Endocrinology
|May 25, 2006
PubMed

Insights

Unliganded thyroid hormone receptors (apoTRs) activate transcription of the Necdin gene via a negative thyroid hormone response element (nTRE). This mechanism involves retinoic X receptor and corepressors, independent of coactivators.

Area of Science:

  • Molecular Endocrinology
  • Gene Regulation
  • Neurodevelopmental Disorders

Background:

  • Unliganded thyroid hormone receptors (apoTRs) typically repress gene transcription by recruiting corepressors.
  • However, apoTRs can activate transcription on promoters with specific negative thyroid hormone response elements (nTREs).

Purpose of the Study:

  • To investigate the role of thyroid hormone in regulating Necdin gene transcription.
  • To elucidate the molecular mechanism of apoTR-mediated activation of the Necdin gene promoter.

Main Methods:

  • Analysis of the Necdin gene promoter for nTRE identification.
  • Investigation of the role of retinoic X receptor (RXR) and corepressors (NCoR/SMRT) in Necdin gene activation.
  • Assessment of the influence of deacetylase activity on Necdin expression.

Main Results:

  • Thyroid hormone regulates Necdin gene transcription through an nTRE located downstream of the transcription start site.
  • Activation of Necdin expression by apoTRs requires RXR and NCoR/SMRT, but not p160 coactivators.
  • Necdin expression is influenced by deacetylase activity, highlighting the context-dependent role of corepressors and histone deacetylases.

Conclusions:

  • The Necdin gene represents a novel target for ligand-independent activation by apoTRs via an nTRE.
  • This mechanism, involving RXR and corepressors, provides insights into the regulation of developmentally important genes like Necdin.
  • Corepressors and histone deacetylases can function as transcriptional activators depending on the specific promoter context.

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