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  • Oral presentation
  • Open Access

Induction of 8-oxoguanine DNA Glycosylase 1 Gene Expression by HIV-1 Tat

Retrovirology20052(Suppl 1):S142

Published: 8 December 2005


Chromatin ImmunoprecipitationmRNA StabilityCellular GeneImmunoprecipitation AssayGenetic Integrity

In order to identify the cellular gene target for Tat, we have performed gene expression profile analysis and found that Tat upregulates the expression of 8-oxoguanine DNA glycosylase (OGG1) gene, encoding an enzyme responsible for repairing the oxidatively damaged guanine, 7,8-dihydro-8-oxoguanine (8-oxo-dG). We observed that Tat induces OGG1 gene expression by enhancing its promoter activity without changing the mRNA stability. We found that the upstream AP-4 site within the OGG1 promoter is responsible and that Tat interacts with AP-4 and removes AP-4 from OGG1 promoter by in vivo chromatin immunoprecipitation assay. Thus, Tat appears to activate OGG1 expression by sequestrating AP-4. Interestingly, although Tat induces oxidative stress known to generate 8-oxo-dG that causes the G:C to T:A transversion, we observed that the amount of 8-oxo-dG was reduced by Tat. When OGG1 was knocked-down by small interfering RNA (siRNA), Tat increased the amount of 8-oxo-dG, thus confirming the role of OGG1 in preventing the formation of 8-oxo-dG. These findings collectively indicate a possibility that Tat may play a role in the maintenance of genetic integrity of the proviral and host cellular genomes by upregulating OGG1 as a feed-forward mechanism.


Authors’ Affiliations

Dept. Mol. Cell. Biology, Nagoya City University Graduate School of Medical Sciences, and Dept. Env. Oncol., University of Occupational and Environmental Health, Japan


© The Author(s) 2005