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

Publication ,  Journal Article
Wang, D; Xia, X; Liu, Y; Oetting, A; Walker, RL; Zhu, Y; Meltzer, P; Cole, PA; Shi, Y-B; Yen, PM
Published in: Mol Endocrinol
May 2009

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 TSHalpha 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 TSHalpha promoter. T(3) also caused release of a corepressor complex composed of histone deacetylase 3 (HDAC3), transducin beta-like protein 1, and nuclear receptor coprepressor (NCoR)/ silencing mediator for retinoic and thyroid hormone receptor from TSHalpha 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 TSHalpha gene expression and show that similar complexes and overlapping epigenetic modifications can participate in both negative and positive transcriptional regulation.

Duke Scholars

Published In

Mol Endocrinol

DOI

EISSN

1944-9917

Publication Date

May 2009

Volume

23

Issue

5

Start / End Page

600 / 609

Location

United States

Related Subject Headings

  • Triiodothyronine
  • Transducin
  • Repressor Proteins
  • Receptors, Thyroid Hormone
  • Rats
  • Protein Binding
  • Promoter Regions, Genetic
  • Polymerase Chain Reaction
  • Oligonucleotide Array Sequence Analysis
  • Histones
 

Citation

APA
Chicago
ICMJE
MLA
NLM
Wang, D., Xia, X., Liu, Y., Oetting, A., Walker, R. L., Zhu, Y., … Yen, P. M. (2009). Negative regulation of TSHalpha target gene by thyroid hormone involves histone acetylation and corepressor complex dissociation. Mol Endocrinol, 23(5), 600–609. https://doi.org/10.1210/me.2008-0389
Wang, Dongqing, Xianmin Xia, Ying Liu, Alexis Oetting, Robert L. Walker, Yuelin Zhu, Paul Meltzer, Philip A. Cole, Yun-Bo Shi, and Paul M. Yen. “Negative regulation of TSHalpha target gene by thyroid hormone involves histone acetylation and corepressor complex dissociation.Mol Endocrinol 23, no. 5 (May 2009): 600–609. https://doi.org/10.1210/me.2008-0389.
Wang D, Xia X, Liu Y, Oetting A, Walker RL, Zhu Y, et al. Negative regulation of TSHalpha target gene by thyroid hormone involves histone acetylation and corepressor complex dissociation. Mol Endocrinol. 2009 May;23(5):600–9.
Wang, Dongqing, et al. “Negative regulation of TSHalpha target gene by thyroid hormone involves histone acetylation and corepressor complex dissociation.Mol Endocrinol, vol. 23, no. 5, May 2009, pp. 600–09. Pubmed, doi:10.1210/me.2008-0389.
Wang D, Xia X, Liu Y, Oetting A, Walker RL, Zhu Y, Meltzer P, Cole PA, Shi Y-B, Yen PM. Negative regulation of TSHalpha target gene by thyroid hormone involves histone acetylation and corepressor complex dissociation. Mol Endocrinol. 2009 May;23(5):600–609.

Published In

Mol Endocrinol

DOI

EISSN

1944-9917

Publication Date

May 2009

Volume

23

Issue

5

Start / End Page

600 / 609

Location

United States

Related Subject Headings

  • Triiodothyronine
  • Transducin
  • Repressor Proteins
  • Receptors, Thyroid Hormone
  • Rats
  • Protein Binding
  • Promoter Regions, Genetic
  • Polymerase Chain Reaction
  • Oligonucleotide Array Sequence Analysis
  • Histones