Genomic organization and expression of the human tumorous imaginal disc (TID1) gene

Human Tid-1, the human homologue of the Drosophila tumor suppressor lethal (2) tumorous imaginal discs, l(2) tid gene product, is a member of the DNAJ family of proteins which serve as co-chaperones to Hsp70 proteins. Here we report the cloning and characterization of the genomic structure of the human TID1 gene (hTID1), which is located on chromosome 16p13.3. hTID1 is approximately 34 kb and is composed of 12 exons. Exon sizes vary from 64 to 232 nucleotides, with the exception of exon 12 corresponding to the 3' untranslated region of hTID1, which extends over 1.1 kb. S1 nuclease protection assays and primer extension experiments indicate a putative transcriptional start site 21 nucleotides upstream of the initiating methionine. The presumptive promoter is characterized by the lack of TATA and CAAT motifs, and a high G+C content. The 5' flanking region contains several consensus binding sites for transcription factors that regulate gene expression during tissue and organ development, such as myeloid zinc finger (MZF1), Ikaros 2 and homeodomain proteins, as well as factors implicated in cell growth and survival responses, including AP-1, PEA3, E2F and NF-kB. Three alternatively spliced variants of hTID1 are expressed in a tissue and cell-type specific manner in many of the human tissues examined. The existence of these forms needs to be considered in efforts aimed at identifying mutations in the hTID1 gene.