MOUSE INTERLEUKIN-2 RECEPTOR-ALPHA GENE-EXPRESSION - INTERLEUKIN-1 AND INTERLEUKIN-2 CONTROL TRANSCRIPTION VIA DISTINCT CIS-ACTING ELEMENTS

We have shown that interleukin-1 (IL-1) and IL-2 control IL-2 receptor alpha (IL-2R alpha) gene transcription in CD4(-)CD8(-) murine T lymph ocyte precursors, Here we map the cis acting elements that mediate int erleukin responsiveness of the mouse IL-2R alpha gene using a thymic l ymphoma-derived hybridoma (PC60), The transcriptional response of the IL-2R alpha gene to stimulation by IL-1 + IL-2 is biphasic, IL-1 induc es a rapid, protein synthesis-independent appearance of IL-2R alpha mR NA that is blocked by inhibitors of NF-kappa B activation, It also pri mes cells to become IL-2 responsive and thereby prepares the second ph ase, in which IL-2 induces a 100-fold further increase in IL-2R alpha transcripts. Transient transfection experiments show that several elem ents in the promoter-proximal region of the IL-2R alpha gene contribut e to IL-1 responsiveness, most importantly an NF-kappa B site conserve d in the human and mouse gene, IL-2 responsiveness, on the other hand, depends on a 78-nucleotide segment 1.3 kilobases upstream of the majo r transcription start site, This segment functions as an IL-2-inducibl e enhancer and lies within a region that becomes DNase I hypersensitiv e in normal T cells in which IL-2R alpha expression has been induced, IL-2 responsiveness requires three distinct elements within the enhanc er. Two of these are potential binding sites for STAT proteins.