Role of chromatin disruption and histone acetylation in thyroid hormone receptor action: implications in the regulation of HIV-1 LTR

S.C.V. Hsia, A. Tomita, K. Obata, B. Paul, D. Buchholz and Y.-B. Shi

Laboratory of Gene Regulation and Development, National Institute of Child Health and Human Development,
National Institutes of Health, Bethesda, Maryland, USA

Offprint requests to: Dr. Yun-Bo Shi, Laboratory fof Gene Regulation and Development, Building 18 T, Rm 106, National Institute of Child Health and Human Development, National Institute of Health, Bethesda, MD, 208092, USA. Fax: (301) 402-1323. e-mail: shi@helix.nih.gov

 

Summary. Thyroid hormone (TH) affects a wide variety of biological processes, from development to physiological function of different cells and organs. Alterations in plasma TH concentrations lead to developmental abnormalities and pathological consequences. Earlier studies have observed that plasma TH levels vary in AIDS patients such that low levels of TH correlate with survival rate. Furthermore, studies on the regulation of the human immunodeficiency virus type 1 (HIV-1) have shown that TH receptor (TR) is capable of binding to two regions within the long terminal repeat (LTR), which controls the transcription of HIV-1 genome. The frog oocyte is an in vivo system that allows microinjected DNA to be chromatinized in a process mimicking the process that occurs in somatic cells. Studies in the frog oocyte have provided in vivo evidence on the role of chromatin remodeling in transcriptional regulation by TR and have shown that TR utilizes similar mechanisms in the regulation of the HIV-1 LTR. That is, TR binds to LTR in chromatin in vivo and represses the LTR in the absence of TH by recruiting corepressor complexes containing histone deacetylases, and upon TH binding, TR causes chromatin remodeling and LTR activation. Histol. Histopathol. 18, 323-331 (2003)

Key words: Thyroid hormone receptor, HIV, AIDS, Chromatin, Histone acetylation

DOI: 10.14670/HH-18.323