Dynamic binding of Ku80, Ku70 and NF90 to the IL-2 promoter in vivo in activated T-cells.
IL-2 gene expression in activated T-cells is initiated by chromatin remodeling at the IL-2 proximal promoter and conversion of a transcriptional repressor into a potent transcriptional activator. A purine-box regulator complex was purified from activated Jurkat T-cell nuclei based on sequence-specific DNA binding to the antigen receptor response element (ARRE)/nuclear ... factor of activated T-cells (NF-AT) target DNA sequence in the proximal IL-2 promoter. ARRE DNA-binding subunits were identified as NF90, NF45 and systemic lupus erythematosis autoantigens, Ku80 and Ku70. Monoclonal antibodies to Ku80, Ku70 and NF90 specifically inhibit constitutive and inducible ARRE DNA-binding activity in Jurkat T-cells. Ku80, Ku70 and NF90 bind specifically to the IL-2 gene promoter in vivo, as demonstrated by chromatin immunoprecipitation. Activation of Jurkat T-cells and mouse primary spleen cells induces binding of Ku80 and NF90 to the IL-2 promoter in vivo, and decreases binding of Ku70 to the IL-2 promoter in vivo, and these dynamic changes are inhibited by immunosuppressants cyclosporin A and triptolide. Dynamic changes in binding of Ku80, Ku70 and NF90 to the IL-2 proximal promoter in vivo correlate with chromatin remodeling and transcriptional initiation in activated T-cells.
Mesh Terms:
Animals, Antigens, Nuclear, Binding Sites, Cells, Cultured, Chromatin Immunoprecipitation, Cyclosporine, DNA-Activated Protein Kinase, DNA-Binding Proteins, Diterpenes, Epoxy Compounds, Humans, Immunosuppressive Agents, Interleukin-2, Jurkat Cells, Lymphocyte Activation, Mice, Mice, Inbred C57BL, Nuclear Factor 45 Protein, Nuclear Factor 90 Proteins, Phenanthrenes, Promoter Regions, Genetic, Protein Subunits, Response Elements, T-Lymphocytes
Animals, Antigens, Nuclear, Binding Sites, Cells, Cultured, Chromatin Immunoprecipitation, Cyclosporine, DNA-Activated Protein Kinase, DNA-Binding Proteins, Diterpenes, Epoxy Compounds, Humans, Immunosuppressive Agents, Interleukin-2, Jurkat Cells, Lymphocyte Activation, Mice, Mice, Inbred C57BL, Nuclear Factor 45 Protein, Nuclear Factor 90 Proteins, Phenanthrenes, Promoter Regions, Genetic, Protein Subunits, Response Elements, T-Lymphocytes
Nucleic Acids Res.
Date: Mar. 29, 2007
PubMed ID: 17389650
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