Genomic organization and characterization of the promoter of the human ATP-binding cassette transporter-G1 (ABCG1) gene

The ATP-binding cassette transporter G1 (ABCG1) was recently identified as a regulator of macrophage cholesterol and phospholipid transport. This tran sporter together with ABCA1 belongs to a group of sterol-sensitive ABC prot eins which are induced by lipid loading or specific oxysterols. We report h ere the genomic structure of ABCG1 along with the 5' flanking sequence usin g library screening and BLAST search analysis. The ABCG1 gene spans more th an 70 kb and contains 15 exons. The exon size is between 30 and 1081 bp and the introns range in size from 137 bp to more than 45 kb. All exon-intron boundaries display the canonical GT/AG sequences. Using promoter-luciferase reporter assays in the myeloid cell lines THP-1 and RAW246.7 and the hepat oma cell line HepG2 we could demonstrate the functionality of the ABCG1 pro moter and the minimal sequence requirements for gene expression. The TATA-l ess proximal promoter contains multiple Sp1 binding sites and a consensus s equence for sterol regulatory element binding protein. (C) 2000 Elsevier Sc ience B.V. All rights reserved.