Transcriptional repressor DREAM regulates T-lymphocyte proliferation and cytokine gene expression.
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.
Savignac
Magali
M
Departamento de Biología Molecular y Celular, Centro Nacional de Biotecnología, Consejo Superior de Investigaciones Cientificas, Madrid, Spain.
Pintado
Belen
B
Gutierrez-Adan
Alfonso
A
Palczewska
Malgorzata
M
Mellström
Britt
B
Naranjo
Jose R
JR
D000818:Animals; D049109:Cell Proliferation; D047369:Chromatin Immunoprecipitation; D016207:Cytokines / Q000235:genetics* / Q000378:metabolism; D015536:Down-Regulation; D005786:Gene Expression Regulation; D006801:Humans; D051605:Kv Channel-Interacting Proteins / Q000235:genetics / Q000378:metabolism*; D008213:Lymphocyte Activation / Q000235:genetics*; D051379:Mice; D008822:Mice, Transgenic; D011948:Receptors, Antigen, T-Cell / Q000819:agonists; D012097:Repressor Proteins / Q000235:genetics / Q000378:metabolism*; D013601:T-Lymphocytes / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D014158:Transcription, Genetic; D015854:Up-Regulation
D016207:Cytokines; C496749:KCNIP3 protein, human; D051605:Kv Channel-Interacting Proteins; D011948:Receptors, Antigen, T-Cell; D012097:Repressor Proteins