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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


  • John S
  • Reeves RB
  • Lin JX
  • Child R
  • Leiden JM
  • Thompson CB
  • Leonard WJ


Molecular and cellular biology

Publication Data

March 23, 1995

Associated Grants

  • Agency: NIAID NIH HHS, Id: R01 AI29673

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