Unknown,Transcriptomics,Genomics,Proteomics

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Genome-wide binding map of the HIV Tat protein to the human genome (gene expression)

ABSTRACT: The HIV-1 Trans-Activator of Transcription (Tat) protein binds to multiple host cellular factors and greatly enhances the level of transcription of the HIV genome. Here, we report the genome-wide binding map of Tat to the human genome in Jurkat T cells (Jurkat-Tat cells) using chromatin immunoprecipitation combined with next-generation sequencing. cDNA microarray was used to monitor gene expression changes between Jurkat and Jurkat-Tat cells. Additionally, we compared distribution of H3K9ac near gene promoters between Jurkat and Jurkat-Tat cells using ChIP-chip method and hybridized onto Agilent promoter array. Our data reveal that Tat’s interaction with the host genome is more extensive than previously thought, with potentially important implications for the viral life cycle. Agilent gene expression microarray was used to compare gene expression changes between Jurkat T cells and Jurkat T cells expressing HIV-Tat protein (Jurkat-Tat T cells) Expression profiles on Jurkat-Tat cells versus Jurkat cells. ChIP on chip for H3K9ac in Jurkat-Tat versus Jurkat cells. ChIP-seq for HIV-1 Tat protein in Jurkat-Tat cells.

ORGANISM(S): Homo sapiens

SUBMITTER: Siavash Kurdistani

PROVIDER: E-GEOD-30734 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Project description:Our previous work demonstrated that HIV-1 infection progressively reduces TCR/CD3 expression due to a defect in CD3g gene transcripts. We further found that knocking down expression of the viral tat and/or nef genes was correlated with CD3g transcript and TCR/CD3 surface receptor levels on HIV-1 infected cells. This study was undertaken to investigate the direct effect of HIV-1 Tat expression on the TCR/CD3 machinery. Progressive downregulation from TCR/CD3hi to TCR/CD3lo to TCR/CD3â was observed on Tat expressing cells in a manner that emulated HIV-1 infection, with a lack of CD3g transcripts again responsible for the defect. When Tat cell cultures containing a mixture of TCR/CD3 surface densities were separated into TCR/CD3hi and TCR/CD3lo/â populations, they quickly reverted to a mixed CD3 phenotype. Thus, the progression TCR/CD3hi to TCR/CD3lo to TCR/CD3â is an active, reversible process with receptor levels fluctuating in response to intracellular dynamics. Examination of tat mutants found that the regions involved in Tat-mediated transactivation and TAR binding are required for TCR/CD3 downregulation while the lysine at position 28 and Tat exon 2 are dispensable. Global gene expression, assessed in association with TCR/CD3 downregulation in HIV-1 infected and Tat expressing cells, detected broad suppression of TCR/CD3 signaling, co-stimulation and negative regulatory genes along with target transcription factors, ligands and receptors. A significant subset of the genes altered in HIV-1 infected cells was specifically targeted by Tat in association with TCR/CD3 loss. Our finding that Tat negatively regulates many facets of the TCR/CD3 machinery has important implications for disease pathogenesis. We used microarrays to investigate changes in CD4+ T cell gene expression induced by expression of the HIV-1 Tat protein. Examine changes in gene expression in HIV-1 Tat transduced cells compared with cells transduced with an antisense Tat sequence used as a control.

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Genome-wide binding map of the HIV Tat protein to the human genome (gene expression)

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