Cell-type-restricted binding of the transcription factor NFAT to a distal IL-4 enhancer in vivo. NLM AIDSLINE Important note: Information in this article was accurate in 2000. The state of the art may have changed since the publication date.

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Cell-type-restricted binding of the transcription factor NFAT to a distal IL-4 enhancer in vivo.

Immunity. 2000 Jun;12(6):643-52. Unique Identifier : AIDSLINE MED/20350662
Agarwal S; Avni O; Rao A; Department of Pathology, Harvard Medical School and the Center; for Blood Research, Boston, Massachusetts 02115, USA.


Abstract: By DNase I hypersensitivity analysis, we have identified an inducible, cyclosporin A-sensitive enhancer located 3' of the interleukin-4 (IL-4) gene. The enhancer binds the Th2-specific transcription factor GATA3 in vivo but is not perceptibly influenced by the absence of a second Th2-specific factor, cMaf. The antigen-inducible transcription factor NFAT1 binds the IL-4 enhancer and the IL-4 promoter only in stimulated Th2 cells; conversely, NFAT1 binds to the interferon (IFN)-gamma promoter only in stimulated Th1 cells. Our results support a model whereby transcription factors such as NFAT1, which are nonselectively induced in antigen-stimulated T cells, gain access to cytokine regulatory regions only in the appropriate subset of differentiated T cells in vivo. This restricted access enables antigen-dependent and subset-specific transcription of cytokine genes.
Keywords: JOURNAL ARTICLE Animal Base Sequence Binding Sites/DRUG EFFECTS/GENETICS/IMMUNOLOGY Clone Cells Cyclosporine/PHARMACOLOGY Cytokines/GENETICS Deoxyribonuclease I/METABOLISM DNA-Binding Proteins/*METABOLISM/PHYSIOLOGY Enhancer Elements (Genetics)/DRUG EFFECTS/*IMMUNOLOGY Gene Expression Regulation/DRUG EFFECTS/IMMUNOLOGY Interleukin-4/GENETICS/*METABOLISM Mice Mice, Inbred C57BL Molecular Sequence Data Proto-Oncogene Proteins/PHYSIOLOGY Regulatory Sequences, Nucleic Acid/DRUG EFFECTS/IMMUNOLOGY Support, Non-U.S. Gov't Support, U.S. Gov't, P.H.S. Th2 Cells/DRUG EFFECTS/METABOLISM Trans-Activators/METABOLISM Transcription Factors/*METABOLISM 3' Untranslated Regions/DRUG EFFECTS/METABOLISMKWDjournalarticleanimalbasesequencebindingsites/drugeffects/genetics/immunologyclonecellscyclosporine/pharmacologycytokines/geneticsdeoxyribonucleasei/metabolismdna-bindingproteins/KWDmetabolism/physiologyenhancerelements(genetics)/drugeffects/KWDimmunologygeneexpressionregulation/drugeffects/immunologyinterleukin-4/genetics/KWDmetabolismmicemice,inbredc57blmolecularsequencedataproto-oncogeneproteins/physiologyregulatorysequences,nucleicacid/drugeffects/immunologysupport,non-uKWDsKWDgov'tsupport,uKWDsKWDgov't,pKWDhKWDsKWDth2cells/drugeffects/metabolismtrans-activators/metabolismtranscriptionfactors/KWDmetabolism3'untranslatedregions/drugeffects/metabolism
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