Transcriptional repressor DREAM regulates T-lymphocyte proliferation and cytokine gene expression
Downstream Regulatory Element Antagonist Modulator (DREAM) is a Ca 2+-dependent transcriptional repressor expressed in the brain, thyroid gland and thymus. Here, we analyzed the function of DREAM and the related protein KChIP-2 in the immune system using transgenic (tg) mice expressing a cross-dominant active mutant (EFmDREAM) for DREAM and KChIPs Ca2+-dependent transcriptional derepression. EFmDREAM tg mice showed reduced T-cell proliferation. Tg T cells exhibited decreased interleukin (IL)-2, -4 and interferon (IFN)γ production after polyclonal activation and following antigen-specific response. Chromatin immunoprecipitation and transfection assays showed that DREAM binds to and represses transcription from these cytokine promoters. Importantly, specific transient knockdown of DREAM or KChIP-2 induced basal expression of IL-2 and IFNγ in wild-type splenocytes. These data propose DREAM and KChIP-2 as Ca2+-dependent repressors of the immune response. © 2005 European Molecular Biology Organization | All Rights Reserved.
| Main Authors: | , , , , , |
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| Format: | journal article biblioteca |
| Language: | English |
| Published: |
EMBO Press
2005
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| Subjects: | Ca2, Cytokine, DREAM, T lymphocytes, Transcription, |
| Online Access: | http://hdl.handle.net/20.500.12792/4263 http://hdl.handle.net/10261/294602 |
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