Abstract
After entry into the target cell and reverse transcription, HIV-1 genes are integrated into the host genome. It is now well established that the viral promoter activity is directly governed by its chromatin environment. Nuc-1, a nucleosome located immediately downstream of the HIV-1 transcriptional initiation site directly impedes long-terminal repeat (LTR) activity. Epigenetic modifications and disruption of Nuc-1 are a prerequisite to the activation of LTR-driven transcription and viral expression. The compaction of chromatin and its permissiveness for transcription are directly dependent on the post-translational modifications of histones such as acetylation, methylation, phosphorylation and ubiquitination. Understanding the molecular mechanisms underlying HIV-1 transcriptional silencing and activation is thus a major challenge in the fight against AIDS and will certainly lead to new therapeutic tools.
Publication types
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Research Support, Non-U.S. Gov't
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Review
MeSH terms
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Azepines / pharmacology
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DNA Methylation / physiology*
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Epigenesis, Genetic / drug effects
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Epigenesis, Genetic / physiology*
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Gene Expression Regulation, Viral / drug effects
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Gene Expression Regulation, Viral / physiology*
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HIV Infections / drug therapy
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HIV Infections / metabolism*
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HIV-1 / genetics
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HIV-1 / physiology*
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Histone Acetyltransferases / metabolism
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Histone Deacetylase Inhibitors / pharmacology
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Histone Deacetylases / metabolism
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Histone-Lysine N-Methyltransferase / antagonists & inhibitors
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Histones / metabolism*
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Humans
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Nucleosomes / metabolism*
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Phorbol Esters / pharmacology
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Piperazines / pharmacology
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Quinazolines / pharmacology
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Transcription, Genetic / physiology*
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Virus Integration / physiology
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tat Gene Products, Human Immunodeficiency Virus / metabolism
Substances
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Azepines
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BIX 01294
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Histone Deacetylase Inhibitors
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Histones
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Nucleosomes
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Phorbol Esters
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Piperazines
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Quinazolines
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tat Gene Products, Human Immunodeficiency Virus
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chaetocin
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prostratin
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Histone-Lysine N-Methyltransferase
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Histone Acetyltransferases
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Histone Deacetylases