TRANSCRIPTION OF THE INTERLEUKIN-1 RECEPTOR-RELATED T1 GENE IS INITIATED AT DIFFERENT PROMOTERS IN MAST-CELLS AND FIBROBLASTS

The delayed early serum response gene T1 encodes glycoproteins of the immunoglobulin superfamily with significant sequence similarity to the type 1 interleukin-1 receptor. The T1 gene is transcribed in fibrobla sts into an abundant 2.7-kilobase (kb) and a rare 5-kb mRNA in respons e to proliferation-inducing stimuli. It gives predominantly rise to th e longer transcript in the bone marrow of adult mice and in cultured m ast cells. Alternative 3' processing is responsible for the two mRNA f orms. The short transcript encodes a secreted protein with marked simi larity to the extracellular domain of the interleukin-1 receptor, wher eas the long mRNA is translated into a protein with an additional puta tive transmembrane and an intracellular domain. Here we demonstrate th at T1 transcription in mast cells and fibroblasts initiates at two dif ferent start sites which are 10.5 kb apart. The alternative first exon s are both spliced to exon 2 which contains the translation start site . Northern blot analysis and primer extension experiments revealed tha t promoter usage is strictly cell type-specific. T1 transcription in m ast cells is initiated exclusively at the distal promoter, whereas in fibroblasts both the short and the long T1 mRNA start at the proximal promoter. Two GATA-1 elements were identified in the 5'-flanking regio n of the mast cell-specific distal exon 1.