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15280353
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To better understand the control of T helper (TH) 1-expressed genes, we compared and contrasted acetylation and expression for three key genes, IFNG, TBET, and IL18RAP and found them to be distinctly regulated.
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15280353
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The TBET and the IFNG genes, but not the IL18RAP gene, showed preferential acetylation of histones H3 and H4 during TH1 differentiation.
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15280353
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Histone H3 acetylation of IFNG and TBET genes occurred with different kinetics, however, and was distinctively regulated by cytokines.
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15280353
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Interleukin (IL)-12 and IL-18 enhanced the histone acetylation of the IFNG gene.
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15280353
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By contrast, histone acetylation of the TBET gene was markedly suppressed by IL-4, whereas IL-12 and IL-18 had only modest effects suggesting that histone acetylation during TH1 differentiation is a process that is regulated by various factors at multiple levels.
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15280353
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By treating Th2 cells with a histone deacetylase inhibitor, we restored histone acetylation of the IFNG and TBET genes, but it did not fully restore their expression in TH2 cells, again suggesting that histone acetylation explains one but not all the aspects of TH1-specific gene expression.
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| 7 |
19464989
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In this issue of Immunity, Schulz et al. (2009) use mathematical modeling to elucidate a signaling network controlling Ifng gene expression, thereby showing the importance of an Interleukin-12-dependent, Interferon-gamma-independent second phase of inducing the transcription factor T-bet.
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| 8 |
21983879
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T-bet orchestrates the differentiation of mature peripheral T-cells into interferon-γ (IFN-γ) and tumor necrosis factor-α producing CD4+ T-helper type I (Th1) and CD8+ T cytotoxic cells that are necessary for antiviral responses.
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21983879
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When IL-12 is produced by antigen-presenting cells, T-bet expression is induced, causing direct stimulation of ifng gene transcription while simultaneously acting as a transcriptional repressor of the IL4 gene, which then leads to Th1 dominance and T-helper type 2 differentiation blockade.
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21983879
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We found that treatment with a farnesyltransferase inhibitor tipifarnib reduced Th1 cytokines in LGL leukemia patient T-cells and blocked T-bet protein expression and IL-12 responsiveness in T-cells from healthy donors.
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