PMID: 8605881Mar 1, 1996Paper

Transcriptional activation and chromatin remodeling of the HIV-1 promoter in response to histone acetylation

The EMBO Journal
Carine Van LintEric M Verdin

Abstract

After integration in the host cell genome, the HIV-1 provirus is packaged into chromatin. A specific chromatin disruption occurs in the HIV-1 promoter during transcriptional activation in response to TNF-alpha, suggesting that chromatin plays a repressive role in HIV-1 transcription and that chromatin modification(s) might result in transcriptional activation. We have treated several cell lines latently infected with HIV-1 with two new specific inhibitors of histone deacetylase, trapoxin (TPX) and trichostatin A (TSA), to cause a global hyperacetylation of cellular histones. Treatment with both drugs results in the transcriptional activation of the HIV-1 promoter and in a marked increase in virus production. Dose-response curves and kinetic analysis show a close correlation between the level of histone acetylation and HIV-1 gene expression. In contrast, both TPX and TSA have little or no effect on HIV-1 promoter activity following transient transfection of an HIV-1 promoter-reporter plasmid. Activation of HIV-1 transcription by TSA and TPX treatment occurs in the absence of NF-kappa B induction. Chromatin analysis of the HIV-1 genome shows that a single nucleosome (nuc-1) located at the transcription start and known to be disru...Continue Reading

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