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 a nd potently induced in T cells in response to mitogenic stimuli. Previ ously, an inducible enhancer between nucleotides -299 and -228 that co ntains NF-kappa B and CArG motifs was identified. We now report the ch aracterization of a second essential positive regulatory element locat ed between nucleotides -137 and -64 that binds Elf-1 and HMG-I(Y). Thi s element had maximal activity in lymphoid cells, paralleling the cell type specificity of Elf-1 expression. Transcription from the IL-2R al pha promoter was inhibited when either the Elf-1 or the HMG-I(Y) bindi ng site was mutated. Coexpression of both proteins activated transcrip tion of the -137 to -64 element in COS-7 cells. Elf-1 physically assoc iated with HMG-I and with NF-kappa B p50 and c-Rel in vitro, suggestin g that protein-protein interactions might functionally coordinate the actions of the upstream and downstream positive regulatory elements. T his is the first report of a physical interaction between an Ets famil y member and NF-kappa B family proteins. These findings provide signif icant new insights into the protein-protein and protein-DNA interactio ns that regulate cell-type-specific and inducible IL-2R alpha gene exp ression and also have implications for other genes regulated by Elf-1 and NF-kappa B family proteins.