Genomic Organization of the Human Fibroblast Growth Factor Receptor 3 (FGFR3) Gene and Comparative Sequence Analysis with the MouseFgfr3Gene

Abstract

Fibroblast growth factor receptor 3 (FGFR3) is a developmentally regulated transmembrane protein. Three other FGFRs (1, 2, and 4) in conjunction with FGFR3 are part of the receptor tyrosine kinase superfamily. Mutations in three of these genes (FGFR1, 2, and 3) have been determined to be the cause of human growth and developmental disorders. We have characterized a 22-kb DNA fragment containing the humanFGFR3gene and determined 11 kb of its nucleotide sequence. The gene consists of 19 exons and 18 introns spanning 16.5 kb, and the boundaries between exons and introns follow the GT/AG rule. The translation initiation and termination 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) contains a CpG island. A comparative sequence analysis of the human and mouseFGFR3genes indicates that the overall genomic structure and organization of the human gene are nearly identical to those of its mouse counterpart. Furthermore, there is a striking similarity in the promoter regions of both genes, and several of the putative transcription factor-binding sites are conserved across species, suggesting a definitive role of these factors in the transcriptional regulation of these genes.