Human apolipoprotein B RNA editing deaminase gene (APOBEC1).

Genomic clones encoding the human APOBEC1 gene and its 5' flanking region have been isolated and characterized. The human gene contains five coding exons. The introns dividing these exons correspond exactly to those found in the mouse gene. The translation initiation site, ATG, is located in exon 2 at the same site as in the mouse. The 5' flanking sequence contains two Alu repeats of the Sq family. Primer extension analysis demonstrated the presence of two major transcription initiation sites. The first transcription initiation site delineates the beginning of a noncoding first exon and resides downstream of the first Alu sequence. The second transcription initiation site is within the second Alu repeat. This Alu repeat resides within the first intron, which is spliced out of the transcript from the first start site. Neither transcription initiation site has a TATA or CCAT box. Comparison with the mouse gene suggests that the Alu sequence insertion split the intestinal promoter and that subsequently the down-stream Alu sequence took on a promoter function. No evidence was found for a far upstream non-tissue-specific promoter similar to that demonstrated in the mouse gene. Rather, consideration of results from the marsupial APOBEC-1 gene suggests that this upstream mouse promoter may have had a later evolutionary origin.