DNA sequences of amelogenin genes provide clues to regulation of expression

The amelogenins are a heterogeneous group of enamel proteins, which have an important function in enamel formation, as mutations in the amelogenin gene result in the enamel defect amelogenesis imperfecta. The cDNAs that encode murine, bovine, human, porcine, rat and opossum amelogenins have been cloned, and as many as nine alternatively spliced messages can be produced from a single primary transcript, explaining some 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 sequences are highly homologous among species. Bovine, murine and human upstream regions also have similarities, with consensus sequences for potential binding of transcription factors, such as AP1 and CTF/NF1. Transgenic 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 upstream regions likely involved in tissue specific regulation of expression, and (c) sequences at the RNA splice sites which may determine exon inclusion or skipping.