GENOMIC ORGANIZATION, EXPRESSION OF THE HUMAN CBFA1 GENE, AND EVIDENCE FOR AN ALTERNATIVE SPLICING EVENT AFFECTING PROTEIN FUNCTION

The Cbfa1 gene, which encodes the transcription factor Osf2/Cbfa1 requ ired for osteoblast differentiation in mouse and human, is mutated in cleidocranial dysplasia, a skeletal dysplasia. We describe here the is olation of the full-length human OSF2/CBFA1 cDNAs, the genomic organiz ation of the entire CBFA1 gene, its expression, and the existence of a n alternative splicing event. Nucleotide sequence analysis of the huma n and mouse OSF2/CBFA1 cDNAs showed a 98% homology in the coding seque nce and 96% in the 5' untranslated (UTR) sequence. Analysis of CBFA1 g enomic clones revealed that the 5' UTR sequence of the human OSF2/CBFA 1 cDNA lies 75 kb upstream of the originally described 5' end of the g ene. The existence of two OSF2/CBFA1 cDNAs is due to an alternative sp licing event around exon 8 that affects the transcriptional activity o f the protein. Northern blot analysis demonstrates that the expression of the human OSF2/CBFA1 gene is restricted to osteoblastic cells.