Expression of ABCG1 regulated by NR1H2,3

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Homo sapiens
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ATP Binding Cassette Subfamily G Member 1 (ABCG1, formerly called “white” and/or ABCG8) expression is induced upon activation of liver X receptors (LXRα/NR1H3 or LXRβ/NR1H2) (Sabol SL et al. 2005; Beyea MM et al. 2007). The ABCG1 gene has been mapped to chromosome 21q22.3 and multiple human ABCG1 transcripts have been detected resulting from different transcription initiation sites and alternative mRNA splicing (Croop JM et al 1997; Langmann T et al. 2000; Lorkowski S et al. 2001; Kennedy MA et al. 2001). Induction of ABCG1 expression by NR1H2,3 agonists likely involves the presence of multiple LXR response elements (LXRE) through the promoter region of the ABCG1 gene (Kennedy MA et al. 2001; Sabol SL et al. 2005; Uehara Y et al. 2007). Studies in ABCG1 knockout mice revealed that ABCG1 is primarily expressed in macrophages, endothelial cells, and lymphocytes. However, it is also found in Kupffer cells and hepatocytes (Kennedy MA et al. 2005). ABCG1 exhibits a tissue specific expression pattern with high expression levels of ABCG1 found in lung, brain, spleen, adrenal glands, heart and liver (Croop JM et al 1997; Klucken J et al. 2000). ABCG1 plays an important role in cholesterol efflux (Kennedy MA et al. 2005; Wang N et al. 2004). In contrast to ABCA1, which transports cholesterol to lipid-poor apolipoprotein acceptors, ABCG1 transports cholesterol to preformed high-density lipoprotein (HDL) particles. A synergistic relationship between ABCA1 and ABCG1 has been proposed, whereby ABCA1 promotes lipidation of lipid-poor apoproteins and thus generating HDL-like acceptors for ABCG1-mediated cholesterol efflux (Gelissen IC et al. 2006). Beyond a role in cellular lipid homeostasis, ABCG1 participates in glucose and lipid metabolism by controlling the secretion and activity of insulin and lipoprotein lipase (Sturek JM et al. 2010; Olivier M et al. 2012; Hardy LM et al. 2017).

G-protein pathway suppressor 2 (GPS2) was identified as a co-regulator required for NR1H2, NR1H3-induced transcription of the ABCG1 gene in human hepatic HepG2 and macrophage THP-1 cells (Jakobsson T et al. 2009).

Literature References
PubMed ID Title Journal Year
19481530 GPS2 is required for cholesterol efflux by triggering histone demethylation, LXR recruitment, and coregulator assembly at the ABCG1 locus

Jakobsson, T, Venteclef, N, Toresson, G, Damdimopoulos, AE, Ehrlund, A, Lou, X, Sanyal, S, Steffensen, KR, Gustafsson, JA, Treuter, E

Mol. Cell 2009
11500512 Characterization of the human ABCG1 gene: liver X receptor activates an internal promoter that produces a novel transcript encoding an alternative form of the protein

Kennedy, MA, Venkateswaran, A, Tarr, PT, Xenarios, I, Kudoh, J, Shimizu, N, Edwards, PA

J. Biol. Chem. 2001
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