The DNA Sequences Required for Apolipoprotein B Expression in the Heart are Distinct from those Required for Expression in the Intestine

We recently reported that the apolipoprotein B (apo-B) gene is expressed in the heart and that the heart secretes apo-B-containing lipoproteins. We have also recently demonstrated that the tissue-specific expression of theapo-Bgene is complex, withapo-Bgene expression in the intestine being dependent on an enhancer element located very far from the structural gene (between 54 and 62 kb 5′ to exon 1). In this study, we investigated whether these distant DNA sequences control or affect the expression of theapo-Bgene in the heart. To address this issue, we analysed heartapo-Bgene expression in heart tissue from a series of humanapo-Btransgenic mice generated from human genomic DNA constructs that ranged in size from 70 to 207 kb. All of these constructs contained the coding portion of theapo-Bgene, but each contained different amounts of flanking sequences (5–120 kb 5′ to the gene and 1.5–35 kb 3′ to the gene). Each construct conferred humanapo-Bgene expression in the heart, including those containing as little as 5 kb of 5′-flanking sequences or as little as 1.5 kb of 3′-flanking sequences. These data support the idea thatapo-Bgene expression in the heart, unlike that in the intestine, is not affected by a distant enhancer element.