Regulation of cell-type-specific interleukin-2 receptor alpha-chain gene expression: potential role of physical interactions between Elf-1, HMG-I(Y), and NF-kappa B family proteins.
The interleukin 2 receptor alpha-chain (IL-2R alpha) gene is rapidly and potently induced in T cells in response to mitogenic stimuli. Previously, an inducible enhancer between nucleotides -299 and -228 that contains NF-kappa B and CArG motifs was identified. We now report the characterization of a second essential positive regulatory ... element located between nucleotides -137 and -64 that binds Elf-1 and HMG-I(Y). This element had maximal activity in lymphoid cells, paralleling the cell type specificity of Elf-1 expression. Transcription from the IL-2R alpha promoter was inhibited when either the Elf-1 or the HMG-I(Y) binding site was mutated. Coexpression of both proteins activated transcription of the -137 to -64 element in COS-7 cells. Elf-1 physically associated with HMG-I and with NF-kappa B p50 and c-Rel in vitro, suggesting that protein-protein interactions might functionally coordinate the actions of the upstream and downstream positive regulatory elements. This is the first report of a physical interaction between an Ets family member and NF-kappa B family proteins. These findings provide significant new insights into the protein-protein and protein-DNA interactions that regulate cell-type-specific and inducible IL-2R alpha gene expression and also have implications for other genes regulated by Elf-1 and NF-kappa B family proteins.
Mesh Terms:
Animals, Base Sequence, Binding Sites, Cell Line, Cell Nucleus, Cercopithecus aethiops, Chloramphenicol O-Acetyltransferase, DNA Primers, DNA-Binding Proteins, Enhancer Elements, Genetic, Gene Expression Regulation, HMGA1a Protein, High Mobility Group Proteins, Humans, Macromolecular Substances, Mice, Molecular Sequence Data, Mutagenesis, Site-Directed, NF-kappa B, Nuclear Proteins, Oligonucleotide Probes, Polymerase Chain Reaction, Receptors, Interleukin-2, Recombinant Proteins, Regulatory Sequences, Nucleic Acid, Sequence Homology, Nucleic Acid, T-Lymphocytes, Tetradecanoylphorbol Acetate, Transcription Factors, Transcription, Genetic, Transfection, Tumor Cells, Cultured
Animals, Base Sequence, Binding Sites, Cell Line, Cell Nucleus, Cercopithecus aethiops, Chloramphenicol O-Acetyltransferase, DNA Primers, DNA-Binding Proteins, Enhancer Elements, Genetic, Gene Expression Regulation, HMGA1a Protein, High Mobility Group Proteins, Humans, Macromolecular Substances, Mice, Molecular Sequence Data, Mutagenesis, Site-Directed, NF-kappa B, Nuclear Proteins, Oligonucleotide Probes, Polymerase Chain Reaction, Receptors, Interleukin-2, Recombinant Proteins, Regulatory Sequences, Nucleic Acid, Sequence Homology, Nucleic Acid, T-Lymphocytes, Tetradecanoylphorbol Acetate, Transcription Factors, Transcription, Genetic, Transfection, Tumor Cells, Cultured
Mol. Cell. Biol.
Date: Mar. 01, 1995
PubMed ID: 7862168
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