Two distinct TATA-less promoters direct tissue-specific expression of the rat Apo-B editing catalytic polypeptide 1 gene

Abstract

The species and tissue specificity of apolipoprotein (apo) B mRNA editing is determined by the expression of apoB editing catalytic polypeptide 1 (APOBEC-1), the cytidine deaminase that catalyzes apoB mRNA editing. To understand the molecular mechanisms that regulate the transcription of APOBEC-1, we characterized rat APOBEC-1 cDNA and genomic DNA. cDNA cloning and RNase protection analysis showed two alternative promoters for the tissue-specific expression of APOBEC-1 in the liver and intestine, P(liv) and P(int). Both promoters lack a TATA box, and P(int) belongs to the MED-1 class of promoters, which initiate transcription at multiple sites. We also identified two allelic forms of the APOBEC-1 gene from the characterization of two rat APOBEC-1 P1 genomic clones, RE4 and RE5. The RE4 allele is 18 kilobases long and contains six exons and five introns, whereas the RE5 allele contains an additional ~8 kilobases of intron sequences and an extra exon encoding a 5'-untranslated region; however, the APOBEC-1 transcripts from the two alleles appear to have similar, if not identical, functions. Transgenic mouse studies showed that P(liv) was preferentially used in the liver, kidney, brain, and adipose tissues, whereas P(int) was preferentially used in the small intestine, stomach, and lung. Our results suggest that the tissue-specific expression of APOBEC-1 is governed by multiple regulatory elements exerting control over a single coding sequence. The presence or absence of these regulatory elements may determine the tissue-specific expression of APOBEC-1 in other mammalian species.