The human ABCG4 gene is regulated by oxysterols and retinoids in monocyte-derived macrophages

Abstract

Here we report the induction of gene expression of ABCG4, a member of the ABC transporter subfamily G, from human macrophages by oxysterols and retinoids, agonists of the nuclear receptors LXR and RXR. The cloned ABCG4 transcript has a size of 3.5 kb and contains an open reading frame which encodes a polypeptide of 646 amino acids. Structurally, the putative ABC transporter protein consists of a nucleotide binding fold followed by a cluster of six transmembrane-spanning domains and thus conforms to the group of half-size ABC transporters. Among the human ABC transporter subfamily G members the novel transporter shows highest protein sequence homology and identity to ABCG1 (84 and 72%, respectively). Analysis of the genomic organization demonstrates that the ABCG4 gene is composed of at least 14 exons which extend across a region of 12.6 kb in size on chromosome 11q23.3. Based on its structural features and an LXR/RXR-responsive regulation similar to the cellular lipid export protein ABCA1, we conclude that ABCG4 may be involved in macrophage lipid homeostasis.