COOPERATIVE INTERACTIONS OF AP-1 AND BASIC HELIX-LOOP-HELIX TRANSCRIPTION FACTORS REGULATE T1 GENE-EXPRESSION

The T1 gene is a murine, delayed early serum-responsive gene that enco des glycoproteins of the interleukin-1 receptor (IL-1R) family. Transc ription of the T1 gene leads to production of two mRNAs that encode a transmembrane protein, which is highly similar to the type-1 IL-1R, an d a secreted protein, which consists solely of the extracellular part. Fibroblasts, in contrast to mast cells, express predominantly the sho rter form of the protein, and several mitogens cause strong, transient induction of the T1 gene in these cells, Here we describe the identif ication of a 148 bp enhancer element that is positioned 3.6 kb upstrea m of the transcription initiation site. A TPA-responsive element (TRE) and three identical E-boxes are located within this sequence. Introdu ced point mutations confirmed the necessity of these sites for full T1 promoter activity, The TRE and the distal E-box are absolutely indisp ensable for promoter function, whereas the two proximal E-boxes contri bute less to promoter strength. In vitro the three E-boxes are bound b y different protein complexes.