Complete coding sequence, promoter region, and genomic structure of the human ABCA2 gene and evidence for sterol-dependent regulation in macrophages

Members of the human ABC transporter A subfamily have gained considerable a ttention based on the recent findings that ABCA1 and ABCR (ABCA4) cause fam ilial HDL-deficiency syndromes and distinct forms of hereditary retinopathi es, respectively. Here we report the complete cDNA and the genomic organiza tion of ABCA2, another member of the human ABC A transporter subfamily. The ABCA2 coding region is 7.3 kb in size and codes for a 2436 amino acid poly peptide that bears the typical features of a full-size ABC transporter. Amo ng the known members of the ABC A subfamily ABCA2 shares highest homology w ith the cholesterol-responsive transporters ABCA1 (50%) and the recently cl oned ABCA7 (44%). The ABCA2 gene comprises 48 exons which are localized wit hin a genomic region of only 21 kb. Analysis of the putative ABCA2 promoter sequence revealed potential binding sites for transcription factors that a re involved in the differentiation of myeloid and neural cells. Gene expres sion analysis in human macrophages showed that ABCA2 mRNA is induced during cholesterol import indicating that ABCA2 is a cholesterol-responsive gene. Our results suggest a potential role for ABCA2 in macrophage lipid metabol ism and neural development. (C) 2001 Academic Press.