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- W67225828 abstract "Abstract IL-21 plays a key role in Th17 differentiation. Interferon (IFN) regulatory factor 4 (IRF4) is a critical regulator of differentiation in B and T cells, and Th17 differentiation is defective in Irf4 KO CD4+ T cells. In B cells, IRF4 is known to cooperatively bind DNA in partnership with the Ets family protein PU.1. However, PU.1 is not expressed in most T cells even though IRF4 is active within these cells, and the functional transcription factor complex that regulates Th17-specific genes was not known. Genome-wide Chip-Seq analysis was used to demonstrate that in T cells, IRF4 binds to a novel composite DNA motif that includes AP1 motifs and which we named AP1-IRF4 composite elements (AICEs). Moreover, IL-21-regulated genes in Th17 cells have co-localized binding of IRF4, BATF, and JUN family proteins, and the genes encoding these transcription factors are themselves regulated by IL-21 in CD4+ T cells. RNA-seq analysis revealed subsets of genes whose regulation by IL-21, either positive or negative, depends on IRF4, and reporter studies demonstrated that IL-21-induced transcription of these genes was dependent on both IRF4 and AP1 transcription factor binding. Our results demonstrate that by utilizing distinct binding partners and DNA sequences, IRF4 mediates cell-type and stimulus-specific functions in multiple lymphocyte lineages." @default.
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- W67225828 date "2013-05-01" @default.
- W67225828 modified "2023-09-25" @default.
- W67225828 title "Elucidation of the mechanism of cell type specific IRF-4-mediated transcription in CD4+ T cells (P1081)" @default.
- W67225828 doi "https://doi.org/10.4049/jimmunol.190.supp.121.12" @default.
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