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 hu man TID1 gene (hTID1), which is located on chromosome 16p13.3. hTID1 is app roximately 34 kb and is composed of 12 exons. Exon sizes vary from 64 to 23 2 nucleotides, with the exception of exon 12 corresponding to the 3' untran slated region of hTID1, which extends over 1.1 kb. S1 nuclease protection a ssays and primer extension experiments indicate a putative transcriptional start site 21 nucleotides upstream of the initiating methionine. The presum ptive promoter is characterized by the lack of TATA and CART motifs, and a high G + C content. The 5' flanking region contains several consensus bindi ng sites for transcription factors that regulate gene expression during tis sue and organ development, such as myeloid zinc finger (MZF1), Ikaros 2 and homeodomain proteins, as well as factors implicated in cell growth and sur vival responses, including AP-1, PEA3, E2F and NF-kappaB. Three alternative ly spliced variants of hTID1 are expressed in a tissue and cell-type specif ic manner in many of the human tissues examined. The existence of these for ms needs to be considered in efforts aimed at identifying mutations in the hTID1 gene. (C) 2001 Elsevier Science B.V. All rights reserved.