First Author | Savignac M | Year | 2005 |
Journal | EMBO J | Volume | 24 |
Issue | 20 | Pages | 3555-64 |
PubMed ID | 16177826 | Mgi Jnum | J:103733 |
Mgi Id | MGI:3610664 | Doi | 10.1038/sj.emboj.7600810 |
Citation | Savignac M, et al. (2005) Transcriptional repressor DREAM regulates T-lymphocyte proliferation and cytokine gene expression. EMBO J 24(20):3555-64 |
abstractText | 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. |