Chromatin disruption in the promoter of human immunodeficiency virus type 1 during transcriptional activation.
Chromatin organization of eukaryotic promoters is increasingly recognized as an important factor in the regulation of transcription in vivo. To determine the role of chromatin in HIV-1 expression, we have examined the nucleosome organization of the promoter of HIV-1 under low and high transcription rates. Independently of the cell line examined, nucleosomes are precisely positioned in the viral 5' long terminal repeat (5' LTR) and define two large nucleosome-free regions encompassing nt 200-450 and 610-720. A nucleosome positioned between these two regions, immediately after the transcription initiation site (nuc-1), is disrupted following TPA or TNF-alpha treatment. The disruption of nuc-1 from DNA is independent of DNA replication since it is completed in 20 min and independent of transcription as it is alpha-amanitin insensitive. A model is proposed in which nuc-1 plays an organizing role in the HIV-1 promoter to bring in close proximity factors bound to DNA in the two nucleosome-free regions, upstream and downstream of the site of transcription initiation. These results define chromatin as an integral component of the HIV-1 transcriptional regulatory machinery and identify a chromatin transition associated with activation of viral gene expression.
Verdin
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Laboratory of Viral and Molecular Pathogenesis, National Institute of Neurological Disorders and Stroke, NIH, Bethesda, MD 20892.
Paras
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P
Van Lint
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C
D000477:Alkylating Agents / Q000494:pharmacology; D000546:Amanitins / Q000494:pharmacology; D001483:Base Sequence; D002460:Cell Line; D002843:Chromatin / Q000502:physiology*; D004261:DNA Replication; D004279:DNA, Viral; D003850:Deoxyribonuclease I / Q000494:pharmacology; D016325:HIV Long Terminal Repeat / Q000235:genetics; D015497:HIV-1 / Q000235:genetics*; D008836:Micrococcal Nuclease / Q000494:pharmacology; D008969:Molecular Sequence Data; D009707:Nucleosomes / Q000378:metabolism; D011401:Promoter Regions, Genetic; D015183:Restriction Mapping; D013463:Sulfuric Acid Esters / Q000494:pharmacology; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D015533:Transcriptional Activation / Q000502:physiology
D000477:Alkylating Agents; D000546:Amanitins; D002843:Chromatin; D004279:DNA, Viral; D009707:Nucleosomes; D013463:Sulfuric Acid Esters; D003850:Deoxyribonuclease I; D008836:Micrococcal Nuclease; C007482:dimethyl sulfate; D013755:Tetradecanoylphorbol Acetate