Transcriptional repressor DREAM regulates T‐lymphocyte proliferation and cytokine gene expression

descriptionPublicationkeyboard_double_arrow_right Article 22 Sep 2005 English Publisher:Springer Science and Business Media LLCJournal:The EMBO Journal, volume 24, pages 3,555-3,564 (issn: 0261-4189, eissn: 1460-2075,

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Authors: Savignac, M.; Pintado, Belén; Gutiérrez-Adán, Alfonso; Palczewska, M.; Mellström, Britt; Naranjo, José Ramón;

doi: 10.1038/sj.emboj.7600810

pmid: 16177826

pmc: PMC1276700

handle: 10261/294602

Transcriptional repressor DREAM regulates T‐lymphocyte proliferation and cytokine gene expression

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Abstract

Downstream Regulatory Element Antagonist Modulator (DREAM) is a Ca2+-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)gamma 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 IFNgamma in wild-type splenocytes. These data propose DREAM and KChIP-2 as Ca2+-dependent repressors of the immune response.

Related Organizations

Spanish National Research Council
Spain
National Center for Biotechnology
Spain

Keywords

Chromatin Immunoprecipitation, Transcription, Genetic, T-Lymphocytes, T lymphocytes, Receptors, Antigen, T-Cell, DREAM, Down-Regulation, Kv Channel-Interacting Proteins, Mice, Transgenic, Lymphocyte Activation, Ca2, Up-Regulation, Repressor Proteins, Mice, Gene Expression Regulation, Animals, Cytokines, Humans, Cytokine, Transcription, Cell Proliferation

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