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Apolipoprotein-AII (apo-AII) is one of a family of evolutionarily related proteins which play a crucial role in lipid transport and metabolism. The serum levels of human apo-AII have been shown to be inversely correlated to the incidence of coronary heart disease and its expression to be limited to the liver and intestine. Here we demonstrate that this dual tissue-specificity involves DNA sequences located in a 259 bp region centred 782 bp upstream from the transcription initiation site. These sequences function in an orientation-independent manner and are absolutely required for transcription from the apo-AII promoter. The regulatory region contains sequences which are homologous to the apo-AI, beta-globin and immunoglobulin gene promoters and to the immunoglobulin heavy-chain enhancer.

The structure and function of the genes encoding the polypeptide components of plasma lipoproteins are of interest because of the central role they play in the regulation of lipid metabolism. We have now completed our previous studies on the human apoAI gene and furthermore isolated and sequenced cDNA clones for apoAII , CII and CIII. The nucleotide sequences show the signal peptides of apoAII , CII and CIII to be 18, 22 and 20 amino acids in length, respectively, and in addition that prepro apoAII bears a classical propeptide structure of 5 amino acids. The amino acid homology detected between apoCII and pro- apoAI is discussed, as is the gene arrangement of the 5' non-coding region of apoAI mRNA. The relative liver mRNA levels of the 4 apolipoproteins analysed in this study have been estimated and compared with their corresponding plasma products. The data reported here provide an essential basis for further studies of structural and functional alleles of apo AI, AII, CII and CIII genes.