The Human ABCG4 Gene Is Regulated by Oxysterols and Retinoids in Monocyte-Derived Macrophages

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...

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Bibliographic Details
Published in:Biochemical and biophysical research communications 2001-10, Vol.288 (2), p.483-488
Main Authors: Engel, Thomas, Lorkowski, Stefan, Lueken, Aloys, Rust, Stephan, Schlüter, Bernhard, Berger, Gudula, Cullen, Paul, Assmann, Gerd
Format: Article
Language:English
Subjects:
ABCA1
ABCA1 protein
ABCG1
ABCG4
ABCG4 gene
Amino Acid Sequence
Animals
ATP Binding Cassette Transporter, Sub-Family G
ATP Binding Cassette Transporter, Sub-Family G, Member 1
ATP-Binding Cassette Transporters - chemistry
ATP-Binding Cassette Transporters - genetics
cholesterol
chromosome 11
Chromosome Mapping
Chromosomes, Human, Pair 11
Cloning, Molecular
differential gene expression
DNA, Complementary - analysis
Exons
foam cell
Gene Expression Regulation - drug effects
Genome, Human
Humans
Introns
LXR
macrophage
Macrophages - drug effects
Macrophages - physiology
Mice
Molecular Sequence Data
Monocytes - physiology
oxysterol
Retinoids - pharmacology
RXR
Sequence Homology, Amino Acid
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Summary: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.
ISSN:0006-291X
1090-2104
DOI:10.1006/bbrc.2001.5756