GENOMIC ORGANIZATION OF THE HUMAN FIBROBLAST GROWTH-FACTOR RECEPTOR-3(FGFR3) GENE AND COMPARATIVE SEQUENCE-ANALYSIS WITH THE MOUSE FGFR3 GENE

Fibroblast growth factor receptor 3 (FGFR3) is a developmentally regul ated transmembrane protein. Three other FGFRs (1, 2, and 4) in conjunc tion with FGFR3 are part of the receptor tyrosine kinase superfamily, Mutations in three of these genes (FGFR1, 2, and 3) have been determin ed to be the cause of human growth and developmental disorders. We hav e characterized a 22-kb DNA fragment containing the human FGFR3 gene a nd determined 11 kb of its nucleotide sequence. The gene consists of 1 9 exons and 18 introns spanning 16.5 kb, and the boundaries between ex ons and introns follow the GT/AG rule,The translation initiation and t ermination sites are located in exon 2 and exon 19, respectively. The sequence of the 5'-flanking region (1.5 kb) lacks the typical TATA or CAAT boxes, However, several putative binding sites for transcription factors SP1, AP2, Krox 24, IgHC.4, and Zeste are present. The 0.77-kb region from position -889 (5'-flanking region) to -119 (intron 1) cont ains a CpG island. A comparative sequence analysis of the human and mo use FGFR3 genes indicates that the overall genomic structure and organ ization of the human gene are nearly identical to those of its mouse c ounterpart. Furthermore, there is a striking similarity in the promote r-regions of both genes, and several of the putative transcription fac tor-binding sites are conserved across species, suggesting a definitiv e role of these factors in the transcriptional regulation of these gen es. (C) 1997 Academic Press.