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.
Pubmed ID: 7862168 RIS Download
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