Involvement of Chromatin and Histone Acetylation in the Regulation of HIV-LTR by Thyroid Hormone Receptor

Cell Res. 2001 Mar;11(1):8-16. doi: 10.1038/sj.cr.7290061.

Abstract

The HIV-1 LTR controls the expression of HIV-1 viral genes and thus is critical for viral propagation and pathology. Numerous host factors have been shown to participate in the regulation of the LTR promoter. Among them is the thyroid hormone (T3) receptor (TR). TR has been shown to bind to the critical region of the promoter that contain the NFbB and Sp1 binding sites. Interestingly, earlier transient transfection studies in tissue culture cells have yielded contradicting conclusions on the role of TR in LTR regulation, likely due to the use of different cell types and/or lack of proper chromatin organization. Here, using the frog oocyte as a model system that allows replication-coupled chromatin assembly, mimicking that in somatic cells, we demonstrate that unliganded heterodimers of TR and RXR (9-cis retinoic acid receptor) repress LTR while the addition of T3 relieves the repression and further activates the promoter. More importantly, we show that chromatin and unliganded TR/RXR synergize to repress the promoter in a histone deacetylase-dependent manner.

MeSH terms

  • Acetylation / drug effects
  • Acquired Immunodeficiency Syndrome / genetics*
  • Acquired Immunodeficiency Syndrome / metabolism
  • Animals
  • Chromatin / drug effects
  • Chromatin / genetics
  • Chromatin / metabolism*
  • Dimerization
  • Gene Expression Regulation, Viral / drug effects
  • Gene Expression Regulation, Viral / genetics*
  • HIV Long Terminal Repeat / drug effects
  • HIV Long Terminal Repeat / genetics*
  • HIV-1 / drug effects
  • HIV-1 / genetics*
  • HIV-1 / metabolism
  • Histone Deacetylases / drug effects
  • Histone Deacetylases / metabolism
  • Histones / drug effects
  • Histones / genetics
  • Histones / metabolism*
  • Ligands
  • NF-kappa B / drug effects
  • NF-kappa B / genetics
  • Oocytes / drug effects
  • Oocytes / metabolism
  • Receptors, Retinoic Acid / genetics
  • Receptors, Retinoic Acid / metabolism
  • Receptors, Thyroid Hormone / genetics*
  • Receptors, Thyroid Hormone / metabolism
  • Response Elements / drug effects
  • Response Elements / genetics
  • Retinoid X Receptors
  • Transcription Factors / genetics
  • Transcription Factors / metabolism
  • Transcription Factors / pharmacology
  • Xenopus laevis

Substances

  • Chromatin
  • Histones
  • Ligands
  • NF-kappa B
  • Receptors, Retinoic Acid
  • Receptors, Thyroid Hormone
  • Retinoid X Receptors
  • Transcription Factors
  • Histone Deacetylases