Unknown,Transcriptomics,Genomics,Proteomics

Dataset Information

Transcription profiling by array of human LPS-activated MM6 cells with Cyclin D1 knockdown

ABSTRACT: Cyclin T1-dependent genes in LPS-activated MM6 cells. HIV-1 is dependent upon cellular co-factors to mediate its replication cycle in CD4+ T cells and macrophages, the two major cell types infected by the virus in vivo. One critical co-factor is Cyclin T1, a subunit of a general RNA polymerase II elongation factor known as P-TEFb. Cyclin T1 is targeted directly by the viral Tat protein to activate proviral transcription. Cyclin T1 is up-regulated when resting CD4+ T cells are activated and during macrophage differentiation or activation, conditions that are also necessary for high levels of HIV-1 replication. Because Cyclin T1 is a subunit of a transcription factor, the up-regulation of Cyclin T1 in these cells results in the induction of cellular genes, some of which might be HIV-1 co-factors. Using shRNA depletions of Cyclin T1 and transcriptional profiling, we identified 54 cellular mRNAs that are Cyclin T1-dependent for their induction in activated CD4+ T cells and during macrophage differentiation and activation. The promoters for these Cyclin T1-dependent genes (CTDGs) are over-represented in two transcription factor binding sites, SREBP1 and ARP1. Notably, 10 of these CTDGs have been reported to be involved in HIV-1 replication, a significant over-representation of such genes when compared to randomly generated lists of 54 genes (p value < 0.00021). SiRNA depletions of two CTDGs identified here, CDK11 and Casein kinase1gamma1, suggest that these genes are also involved in HIV-1 replication. It is therefore likely that the 54 CTDGs identified here include novel HIV-1 co-factors. The presence of CTDGs in the protein space that was available for HIV-1 to sample during its evolution and acquisition of Tat function may provide an explanation for why CTDGs are enriched in viral co-factors. Experiment Overall Design: Using shRNA knockdown of cyclin T1, cyclin T1-dependent genes were identified in LPS-activated MM6 cells.

ORGANISM(S): Homo sapiens

SUBMITTER: Andrew Rice

PROVIDER: E-GEOD-10234 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Publications

Cyclin T1-dependent genes in activated CD4 T and macrophage cell lines appear enriched in HIV-1 co-factors.

Yu Wendong W Ramakrishnan Rajesh R Wang Yan Y Chiang Karen K Sung Tzu-Ling TL Rice Andrew P AP

PloS one 20080905 9

HIV-1 is dependent upon cellular co-factors to mediate its replication cycle in CD4(+) T cells and macrophages, the two major cell types infected by the virus in vivo. One critical co-factor is Cyclin T1, a subunit of a general RNA polymerase II elongation factor known as P-TEFb. Cyclin T1 is targeted directly by the viral Tat protein to activate proviral transcription. Cyclin T1 is up-regulated when resting CD4(+) T cells are activated and during macrophage differentiation or activation, condit ...[more]

PMID: 18773076

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Project description:Parental MM6 cells, as an additional control, were treated with LPS and PMA. Genes affected by the treatments were identified. HIV-1 is dependent upon cellular co-factors to mediate its replication cycle in CD4+ T cells and macrophages, the two major cell types infected by the virus in vivo. One critical co-factor is Cyclin T1, a subunit of a general RNA polymerase II elongation factor known as P-TEFb. Cyclin T1 is targeted directly by the viral Tat protein to activate proviral transcription. Cyclin T1 is up-regulated when resting CD4+ T cells are activated and during macrophage differentiation or activation, conditions that are also necessary for high levels of HIV-1 replication. Because Cyclin T1 is a subunit of a transcription factor, the up-regulation of Cyclin T1 in these cells results in the induction of cellular genes, some of which might be HIV-1 co-factors. Using shRNA depletions of Cyclin T1 and transcriptional profiling, we identified 54 cellular mRNAs that are Cyclin T1-dependent for their induction in activated CD4+ T cells and during macrophage differentiation and activation. The promoters for these Cyclin T1-dependent genes (CTDGs) are over-represented in two transcription factor binding sites, SREBP1 and ARP1. Notably, 10 of these CTDGs have been reported to be involved in HIV-1 replication, a significant over-representation of such genes when compared to randomly generated lists of 54 genes (p value < 0.00021). SiRNA depletions of two CTDGs identified here, CDK11 and Casein kinase1gamma1, suggest that these genes are also involved in HIV-1 replication. It is therefore likely that the 54 CTDGs identified here include novel HIV-1 co-factors. The presence of CTDGs in the protein space that was available for HIV-1 to sample during its evolution and acquisition of Tat function may provide an explanation for why CTDGs are enriched in viral co-factors. Experiment Overall Design: This experiment is part of the big experiments to identify genes specifically affected by cyclin T1 in MM6 cells.

Dataset Information

Transcription profiling by array of human LPS-activated MM6 cells with Cyclin D1 knockdown

Publications

Cyclin T1-dependent genes in activated CD4 T and macrophage cell lines appear enriched in HIV-1 co-factors.

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