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- W1564524120 abstract "Monocyte polarization by IFN-gamma or IL-4 drives a complex series of cellular responses leading to increased intracellular killing (IFN-gamma) or enhanced healing (IL-4) among other functional responses. We studied the effect of IL-4 and IFN-gamma polarization on histone modifications at the TNF-alpha locus in human primary monocytes. IFN-gamma polarization markedly increased the expression of TNF-alpha, whereas IL-4 treatment decreased the expression. We found that IFN-gamma alone increased histone H4 acetylation at the TNF-alpha promoter. The effect of IFN-gamma on TNF-alpha expression was durable upon cytokine washout and even repolarization with IL-4. Concordantly, IFN-gamma-mediated H4 acetylation was also durable. IFN-gamma recruited activating transcription factor-2 via p38 to the TNF-alpha promoter, but inhibition of p38 had minimal effect on H4 acetylation. In a novel finding, we found that IFN-gamma recruited RNA Pol II to the human TNF-alpha promoter via ERK signaling, but did so without initiating transcription, leading to a poised condition. These studies provide an important perspective on monocyte polarization. Polarization by IFN-gamma has a durable effect on TNF-alpha expression, and histone acetylation may provide a mechanism for persistence of the effect." @default.
- W1564524120 created "2016-06-24" @default.
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- W1564524120 date "2008-04-15" @default.
- W1564524120 modified "2023-10-16" @default.
- W1564524120 title "Polarization of Primary Human Monocytes by IFN-γ Induces Chromatin Changes and Recruits RNA Pol II to the TNF-α Promoter" @default.
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- W1564524120 doi "https://doi.org/10.4049/jimmunol.180.8.5257" @default.
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