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Characterization of the Human ABCG1 Gene

Kennedy, Matthew A., Venkateswaran, Asha, Tarr, Paul T., Xenarios, Ioannis, Kudoh, Jun, Shimizu, Nobuyoshi, Edwards, Peter A.·2001·Journal of Biological Chemistry
DOI 10.1074/jbc.m105863200
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Abstract

The human ABCG1 gene encodes a member of the ATP-binding cassette (ABC) superfamily of transporter proteins and is highly induced when macrophages are incubated with oxysterols. Using mRNA from oxysterol-treated human THP-1 cells together with 5'-rapid amplification of cDNA ends and polymerase chain reaction, we identified a novel ABCG1 transcript that encodes a putative protein of 786 residues containing a new amino terminus of 203 amino acids. Characterization of the genomic organization and structure of the human ABCG1 gene demonstrates that: (i) the gene consists of 23 exons spanning 98 kilobase pairs (kb) on chromosome 21q22.3, (ii) the 203 amino acids are encoded on three previously unidentified exons, 8-10, and (iii) a promoter, containing a TATA box and two liver X receptor (LXR) alpha response elements (LXREs), is located upstream of exon 8. Northern analysis using exon-specific probes confirms that oxysterol treatment results in >10-fold induction of ABCG1 transcripts that are derived from either exons 8-23 or exons 5, 7, and 11-23. Electromobility shift assays demonstrate that LXRalpha and retinoid X receptor alpha bind to the two LXREs in intron 7. Cells were transiently transfected with reporter luciferase constructs under the control of either (i) 9 kb of genomic DNA corresponding to intron 7 and part of exon 8 and containing either wild-type or mutant LXREs or (ii) two copies of the wild-type or mutant LXRE. In all cases, the wild-type construct was regulated i…

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  • In response to elevated cellular cholesterol levels, LXRs induce expression of genes involved in cholesterol efflux, including Abca1, Abcg1 and Apoe.

    “In response to elevated cellular cholesterol levels, they function to induce the expression of genes involved in the efflux of cholesterol, including Abca1 and Abcg1 and Apoe (Kennedy et al., 2001; Laffitte et al., 2001; Repa et al., 2000b; Venkateswaran et al., 2000).”

    From Inhibition of cholesterol biosynthesis through RNF145-dependent ubiquitination of SCAP (2017) · cites this paper as Kennedy et al., 2001

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Metadata

Authors
Kennedy, M. A., Venkateswaran, A., Tarr, P. T., Xenarios, I., Kudoh, J., Shimizu, N., & Edwards, P. A.
Venue
Journal of Biological Chemistry
Publisher
Elsevier BV
Published
2001-10
Volume
276
Issue
42
Pages
39438-39447
ISSN
0021-9258
DOI
10.1074/jbc.m105863200
Cited by
217
References
1
Language
en
Licence

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