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Retrovirology  2008 

The histone chaperone protein Nucleosome Assembly Protein-1 (hNAP-1) binds HIV-1 Tat and promotes viral transcription

DOI: 10.1186/1742-4690-5-8

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Abstract:

Using a proteomic screening, we identified hNAP-1 as a novel cellular protein interacting with HIV-1 Tat. We observed that Tat specifically binds hNAP1, but not other members of the same family of factors. Binding between the two proteins required the integrity of the basic domain of Tat and of two separable domains of hNAP-1 (aa 162–290 and 290–391). Overexpression of hNAP-1 significantly enhanced Tat-mediated activation of the LTR. Conversely, silencing of the protein decreased viral promoter activity. To explore the effects of hNAP-1 on viral infection, a reporter HIV-1 virus was used to infect cells in which hNAP-1 had been either overexpressed or knocked-down. Consistent with the gene expression results, these two treatments were found to increase and inhibit viral infection, respectively. Finally, we also observed that the overexpression of p300, a known co-activator of both Tat and hNAP-1, enhanced hNAP-1-mediated transcriptional activation as well as its interaction with Tat.Our study reveals that HIV-1 Tat binds the histone chaperone hNAP-1 both in vitro and in vivo and shows that this interaction participates in the regulation of Tat-mediated activation of viral gene expression.Efficient packaging of DNA in a highly organized chromatin structure inside the cell is one of the most remarkable characteristics of all eukaryotic organisms. Chromatin assembly and disassembly are dynamic biological processes that increase chromatin fluidity and regulate the accessibility of the genome to all DNA transactions, including transcription, DNA replication and DNA repair. The basic structural unit of eukaryotic chromatin is the nucleosome, formed by the wrapping of DNA around an octamer of core histone proteins. By restricting the access to DNA-binding factors and impeding elongation by RNA polymerase II (RNAPII), the nucleosome is not only a structural unit of the chromosome, but perhaps the most important regulator of gene expression (for recent reviews, see refs. [1,

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