DNA-SEQUENCES OF AMELOGENIN GENES PROVIDE CLUES TO REGULATION OF EXPRESSION

The amelogenins are a heterogeneous group of enamel proteins, which ha ve an important function in enamel formation, as mutations in the amel ogenin gene result in the enamel defect amelogenesis imperfecta. The c DNAs that encode murine, bovine, human, porcine, rat and opossum amelo genins have been cloned, and as many as nine alternatively spliced mes sages can be produced from a single primary transcript, explaining som e of the protein heterogeneity. Bovine and human amelogenin genes are found on both X and Y chromosomes, and the sexually dimorphic proteins would have 87-93% identity. A comparison of genes from human, bovine and mouse indicates that they are organized into seven exons, and sequ ences are highly homologous among species. Bovine, murine and human up stream regions also have similarities, with consensus sequences for po tential binding of transcription factors, such as AP1 and CTF/NF1. Tra nsgenic mouse studies have shown that 2300-3500 bp of upstream region are sufficient for expression, while 900 bp are insufficient. Analysis of DNA sequence has identified (a) major homology between species for coding exons with the exception of exon 4, (b) similarities in upstre am regions likely involved in tissue specific regulation of expression , and (c) sequences at the RNA splice sites which may determine exon i nclusion or skipping.