Journal
JOURNAL OF BIOLOGICAL CHEMISTRY
Volume 289, Issue 39, Pages 26752-26761Publisher
AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC
DOI: 10.1074/jbc.M114.587865
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Funding
- German Research Council (Deutsche Forschungsgemeinschaft) [SFB618, SFB TRR52]
- European Research Council Advanced Grants [ERC-2010-AdG_20100317, 268987]
- German Ministry of Education and Research Grant IMPAM [01EC1008B]
- German Ministry of Education and Research e:Bio-Innovationswettbewerb Systembiologie
- European Research Council (ERC) [268987] Funding Source: European Research Council (ERC)
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Th2 memory lymphocytes have imprinted their Il4 genes epigenetically for expression in dependence of T cell receptor restimulation. However, in a given restimulation, not all Th cells with a memory for IL-4 expression express IL-4. Here, we show that in reactivated Th2 cells, the transcription factors NFATc2, NF-kB p65, c-Maf, p300, Brg1, STAT6, andGATA-3assemble at the Il4 promoter in Th2 cells expressing IL-4 but not in Th2 cells not expressing it. NFATc2 is critical for assembly of this transcription factor complex. Because NFATc2 translocation into the nucleus occurs in an all-or-none fashion, dependent on complete dephosphorylation by calcineurin, NFATc2 controls the frequencies of cells reexpressing Il4, translates analog differences in T cell receptor stimulation into a digital decision for Il4 reexpression, and instructs all reexpressing cells to express the same amount of IL-4. This analog-to-digital conversion may be critical for the immune system to respond to low concentrations of antigens.
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