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 NFκB 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.
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Abbreviations
- T3:
-
Thyroid Hormone
- TR:
-
Thyroid Hormone Receptor
- HAT:
-
histone acetyl transferase
- HDAC:
-
histone deacetylase
- TSA:
-
Trichostatin A
- HIV:
-
human immunodeficiency virus
- LTR:
-
Long terminal repeat
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Acknowledgements
We would like to thank Dr. T. Collingwood for the gift of over expressed TR and RXR and Ms. K. Pham for preparing the manuscript.
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HSIA, S., WANG, H. & SHI, Y. Involvement of chromatin and histone acetylation in the regulation of HIV-LTR by thyroid hormone receptor. Cell Res 11, 8–16 (2001). https://doi.org/10.1038/sj.cr.7290061
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DOI: https://doi.org/10.1038/sj.cr.7290061
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