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Molecular and Cellular Biology, June 2002, p. 4043-4052, Vol. 22, No. 12
0270-7306/02/$04.00+0     DOI: 10.1128/MCB.22.12.4043-4052.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.

Chromatin Disruption and Histone Acetylation in Regulation of the Human Immunodeficiency Virus Type 1 Long Terminal Repeat by Thyroid Hormone Receptor

Shao-Chung Victor Hsia and Yun-Bo Shi*

Unit on Molecular Morphogenesis, Laboratory of Gene Regulation and Development, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland 20892-5431

Received 24 September 2001/ Returned for modification 27 November 2001/ Accepted 19 March 2002

The human immunodeficiency virus type 1 (HIV-1) long terminal repeat (LTR) controls the expression of HIV-1 viral genes and thus viral propagation and pathology. Numerous host factors participate in the regulation of the LTR promoter, including thyroid hormone (T3) receptor (TR). In vitro, TR can bind to the promoter region containing the NF-{kappa}B and Sp1 binding sites. Using the frog oocyte as a model system for chromatin assembly mimicking that in somatic cells, we demonstrated that TR alone and TR/RXR (9-cis retinoic acid receptor) can bind to the LTR in vivo independently of T3. Consistent with their ability to bind the LTR, both TR and TR/RXR can regulate LTR activity in vivo. In addition, our analysis of the plasmid minichromosome shows that T3-bound TR disrupts the normal nucleosomal array structure. Chromatin immunoprecipitation assays with anti-acetylated-histone antibodies revealed that unliganded TR and TR/RXR reduce the local histone acetylation levels at the HIV-1 LTR while T3 treatment reverses this reduction. We further demonstrated that unliganded TR recruits corepressors and at least one histone deacetylase. These results suggest that chromatin remodeling, including histone acetylation and chromatin disruption, is important for T3 regulation of the HIV-1 LTR in vivo.

* Corresponding author. Mailing address: Laboratory of Gene Regulation and Development, Building 18 T, Rm. 106, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD 20892. Phone: (301) 402-1004. Fax: (301) 402-1323. E-mail: shi{at}helix.nih.gov.

Molecular and Cellular Biology, June 2002, p. 4043-4052, Vol. 22, No. 12
0022-538X/02/$04.00+0     DOI: 10.1128/MCB.22.12.4043-4052.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.



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