Thyroid hormone-mediated negative transcriptional regulation of Necdin expression. - Archive ouverte HAL Accéder directement au contenu
Article Dans Une Revue Journal of Molecular Endocrinology Année : 2006

Thyroid hormone-mediated negative transcriptional regulation of Necdin expression.

* Nygard M
  • Fonction : Auteur
* Becker N
* Pettersson K
  • Fonction : Auteur
* Bondesson M.
  • Fonction : Auteur

Résumé

Unliganded thyroid hormone receptors (apoTRs) repress transcription of hormone-activated genes by recruiting corepressors to the promoters. In contrast, on promoters containing so-called negative thyroid hormone response elements (nTREs), apoTRs activate transcription. A number of different molecular mechanisms have been described as to how apoTRs activate transcription varying with the target gene of the study. Here we demonstrate that thyroid hormone regulates the transcription of the Necdin gene, a developmentally regulated candidate gene for the genomic imprinting-associated neurobehavioural disorder, Prader-Willi syndrome. ApoTRs activate Necdin expression through an nTRE in its promoter, downstream of the transcription start site. The nTRE of the Necdin gene resembles the nTREs of the TSHbeta genes of the hypothalamus-pituitary-thyroid axis in the sequence, position in the promoter, and mode of activation. We show that this group of nTRE-driven genes shares the requirements for binding of the retinoic X receptor and nuclear receptor corepressor/silencing mediator of retinoid and thyroid hormone receptors (NCoR/SMRT) for full ligand-independent activation, whereas there is no need for association of the p160 family of coactivators. In accordance with the requirement for corepressors, Necdin expression is influenced by deacetylase activity, suggesting that histone deacetylases and corepressors as well could function as activators of transcription, depending on the promoter context.
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Dates et versions

hal-00093448 , version 1 (13-09-2006)

Identifiants

  • HAL Id : hal-00093448 , version 1

Citer

* Nygard M, * Becker N, * Demeneix B, * Pettersson K, * Bondesson M.. Thyroid hormone-mediated negative transcriptional regulation of Necdin expression.. Journal of Molecular Endocrinology, 2006, 36, pp.517 -30. ⟨hal-00093448⟩

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