Exon structure and promoter identification of STIM1 (alias GOK), a human gene causing growth arrest of the human tumor cell lines G401 and RD

The stromal interaction molecular 1 gene (STIM1) encodes a type I trans-mem brane protein of unknown function, which induces growth arrest and degenera tion of the human tumor cell lines G401 and RD but not HBL100 and CaLu-6, s uggesting a role in the pathogenesis of rhabdomyosarcomas and rhabdoid tumo rs. Here, we describe the STIM1 genomic organization Including the identifi cation of the promoter region. The gene consists of 12 exons that span a re gion larger than 250 kb between the genes RRM1 and NUP98. Nucleotide sequen ces of all exon-intron boundaries were determined and oligonucleotide prime rs for the amplification of individual exons were designed. The promoter re gion was identified within a 1.8-kb SacI fragment at the 5' end of the gene . In vitro CpG methylation of the promoter region indicated that transcript ion can be downregulated by this mechanism. The genetic tools developed in the present work will help to determine whether pathogenetic mechanisms tha t associate STIM1 with tumorigenesis involve mutations in coding sequences and/ or promoter, and whether methylation could determine STIM1 transcripti onal down-regulation in tumor samples.