Different promoter usage and multiple transcription initiation sites of the interleukin-1 receptor-related human ST2 gene in UF7 and TM12 cells

The ST2 gene encodes receptor-like molecules that are very similar to the t ype I interleukin-1 receptor. Two distinct types of the ST2 gene products, ST2 (a soluble secreted form) and ST2L (a transmembrane form) are produced by alternative splicing. Here we demonstrate that the human ST2 gene has tw o alternative promoters followed by distinct noncoding first exons, which a re located more than 8 kb apart and are spliced to the common exon 2 contai ning the translation initiation site. Within 1001 bp upstream of the transc ription initiation site of the cloned distal promoter, there are four GATA- 1. The main promoter used for the expression of the ST2 gene in UT-7, a hum an leukaemic cell line, is distinct from that in TM12, a human fibroblastic cell line. Although UT-7 cells use both distal and proximal promoters, the distal promoter is used dominantly for expression of both ST2 and ST2L mRN A. On the other hand, almost all transcription in TM12 cells starts from th e proximal promoter. These results contrast with those of former studies on the rat system, in which ST2 and ST2L mRNA were generated by use of the pr oximal and distal promoters, respectively. Furthermore, UT-7 cells use mult iple transcription initiation sites in both the proximal and distal promote rs, whereas the transcription of the ST2 gene in TM12 cells starts at a uni que site. Intriguingly, these results suggest that ST2 and ST2L proteins ha ve distinct functions in different cells within different biological system s, such as those of growth control, differentiation and immunological respo nses.