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Genomic structure and isoform expression of the mouse, rat and human Cbfa1/Osf2 transcription factor

1998; Elsevier BV; Volume: 214; Issue: 1-2 Linguagem: Inglês

10.1016/s0378-1119(98)00227-3

1879-0038

Zhousheng Xiao, Ronald F. Thomas, T. K. Hinson, L. Darryl Quarles,

RNA Research and Splicing

Although the CBFA1 gene encodes an osteoblast-specific transcription factor that regulates osteoblast differentiation, uncertainty exists about the organization of its 5′ end and the relevance of a novel N-terminal sequence identified in the mouse Cbfa1/Osf2 isoform. We found the novel 5′ Cbfa1/Osf2 sequence is encoded by a previously unrecognized upstream exon, designated exon −1, which is highly conserved in mouse, rat and human. In addition, two splice donor sites may be utilized to generate Cbfa1/Osf2 cDNAs containing different N-terminal sequences. The first ATG and splice donor site in exon −1 is predicted to transcribe a cDNA containing the unique Osf2 5′ sequence, whereas a second donor splice site gives rise to cDNAs that contain sequences encoding an 11 amino acid insert. In the human CBFA1 gene, an additional 2-bp nucleotide insert shifts the reading frame and results in stop codons in the cDNA sequence derived from exon −1. The 5′-most exon of the human CBFA1 gene, therefore, contains the 5′ non-coding region rather than a human OSF2 homolog. The absence of a homologous OSF2 coding sequence in the human CBFA1 cDNA suggests that the novel mouse N-terminal Osf2 sequence is not essential for functioning of the CBFA1 gene product. In addition, multiple transcripts derived from a single CBFA1/Cbfa1 gene were detected in osteoblasts by Northern analysis and RT–PCR, including additional Cbfa1/Osf2 isoforms containing deletions of exons 1 and 4. Thus, the alternative use of transcription start sites and splicing leads to the genesis of CBFA1/Cbfa1 isoforms with possible differences in transactivation potentials.