Negative regulation of tshα target gene by thyroid hormone involves histone acetylation and corepressor complex dissociation

Dongqing Wang, Xianmin Xia, Ying Liu, Alexis Oetting, Robert L. Walker, Yuelin Zhu, Paul Meltzer, Philip A. Cole, Yun Bo Shi, Paul M. Yen

Research output: Contribution to journalArticle

Abstract

Currently, little is known about histone modifications and molecular mechanisms of negatively regulated transcription. In pituitary cells, thyroid hormone (T 3) decreased transcription, and surprisingly increased histone acetylation, of TSHα promoter. This increase was mediated directly by thyroid hormone receptor. Histone acetylation of H3K9 and H3K18 sites, two modifications usually associated with transcriptional activation, occur in negative regulation of TSHα promoter. T 3also caused release of a corepressor complex composed of histone deacetylase 3 (HDAC3), trans- ducin β-like protein 1, and nuclear receptor coprepressor (NCoR)/ silencing mediator for retinoic and thyroid hormone receptor from TSHα promoter in chromatin immunoprecipitation assays. NCoR and HDAC3 overexpression selectively increased ligand-independent basal transcription. Two histone acetyltransferase inhibitors increased overall transcription but did not abrogate negative regulation or NCoR/HDAC3 complex release by T 3. Chromatin immunoprecipitation analyses of an endogenous positively regulated target gene showed increased histone acetylation and corepressor complex release with T 3 treatment. Finally, microarray analyses suggested there is a subset of negatively regulated genes with increased histone acetylation. These findings demonstrate the critical role of NCoR/HDAC3 complex in negative regulation of TSHα gene expression and show that similar complexes and overlapping epigenetic modifications can participate in both negative and positive transcriptional regulation

Original languageEnglish (US)
Pages (from-to)600-609
Number of pages10
JournalMolecular Endocrinology
Volume23
Issue number5
DOIs
StatePublished - May 2009

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Co-Repressor Proteins
Acetylation
Cytoplasmic and Nuclear Receptors
Thyroid Hormones
Histones
Thyroid Hormone Receptors
Histone Deacetylases
Chromatin Immunoprecipitation
Genes
Histone Code
Transducin
Histone Acetyltransferases
Gene Expression Regulation
Microarray Analysis
Epigenomics
Transcriptional Activation
Ligands
histone deacetylase 3
Proteins

ASJC Scopus subject areas

  • Molecular Biology
  • Endocrinology
  • Medicine(all)

Cite this

Negative regulation of tshα target gene by thyroid hormone involves histone acetylation and corepressor complex dissociation. / Wang, Dongqing; Xia, Xianmin; Liu, Ying; Oetting, Alexis; Walker, Robert L.; Zhu, Yuelin; Meltzer, Paul; Cole, Philip A.; Shi, Yun Bo; Yen, Paul M.

In: Molecular Endocrinology, Vol. 23, No. 5, 05.2009, p. 600-609.

Research output: Contribution to journalArticle

Wang, D, Xia, X, Liu, Y, Oetting, A, Walker, RL, Zhu, Y, Meltzer, P, Cole, PA, Shi, YB & Yen, PM 2009, 'Negative regulation of tshα target gene by thyroid hormone involves histone acetylation and corepressor complex dissociation', Molecular Endocrinology, vol. 23, no. 5, pp. 600-609. https://doi.org/10.1210/me.2008-0389
Wang, Dongqing ; Xia, Xianmin ; Liu, Ying ; Oetting, Alexis ; Walker, Robert L. ; Zhu, Yuelin ; Meltzer, Paul ; Cole, Philip A. ; Shi, Yun Bo ; Yen, Paul M. / Negative regulation of tshα target gene by thyroid hormone involves histone acetylation and corepressor complex dissociation. In: Molecular Endocrinology. 2009 ; Vol. 23, No. 5. pp. 600-609.
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