Targeted Derepression of the Human Immunodeficiency Virus Type 1 Long Terminal Repeat by Pyrrole-Imidazole Polyamides

Creators: Coull, Jason J.; He, Guocheng; Melander, Christian; Rucker, Victor C.; Dervan, Peter B.; Margolis, David M.

Abstract

The host factor LSF represses the human immunodeficiency virus type 1 long terminal repeat (LTR) by mediating recruitment of histone deacetylase. We show that pyrrole-imidazole polyamides targeted to the LTR can specifically block LSF binding both in vitro and within cells via direct access to chromatin, resulting in increased LTR expression.

Additional Information

© 2002 American Society for Microbiology. Received 4 June 2002/ Accepted 28 August 2002 We thank H. Johnson for excellent technical assistance. We thank R. Koup and R. Gaynor for advice and J. V. Garcia, D. Sodora, and U. Hansen for advice and careful review. The following reagents were obtained through the AIDS Research and Reference Reagent Program, Division of AIDS, National Institute of Allergy and Infectious Diseases, National Institutes of Health (NIH): HeLaCD4-CAT from Barbara K. Felber and George N. Pavlakis and ACH-2 from Thomas Folks. This work was supported by an NIH postdoctoral grant (GM19789-02) to C.M., an NIH grant (AI 45297) to D.M.M., and an NIH grant (GM51747) to P.B.D.

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