NR1H2,3 binds the APOE gene

Stable Identifier
R-HSA-9031522
Type
Reaction [binding]
Species
Homo sapiens
Compartment
Synonyms
LXR binds the APOE gene
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Apolipoprotein E (APOE), a 34-kD glycoprotein, is involved in lipoprotein clearance by serving as a ligand for the low-density lipoprotein (LDL) receptor family. APOE is primarily lipidated via the ATP-binding cassette transporter A1 (ABCA1), and both are under transcriptional regulation by the liver X receptor α (LXRα or NR1H3) and LXRβ (NR1H2) (Laffitte BA et al. 2001; Beyea MM et al. 2007). The ligand-activated NR1H2 and NR1H3, whose natural ligands are oxysterols, function as obligate heterodimers with retinoid X receptor (RXR) to regulate the expression of target genes through binding to LXR response elements (LXREs) within the regulatory region of their target genes. Both NR1H2:RXRα and NR1H3 :RXRα heterodimers were reported to regulate APOE transcription directly through interaction with conserved LXREs found within tissue-specific enhancer regions (multienhancers ME.1 and ME.2) that confer APOE expression in adipose tissue and macrophages (Shih SJ et al. 2000; Laffitte BA et al. 2001). A low-affinity LXRE was also found in the promoter region of the APOE gene (Laffitte BA et al. 2001). Further, oxysterol-binding protein related protein 1S (ORP1S) was shown to associate with NR1H2 and NR1H3 in the nucleus (Lee S et al. 2012). ORP1S promoted the binding of the receptors to LXREs and specifically enhanced NR1H2,3-dependent transcription of APOE via the ME.1 and ME.2 of the APOE gene (Lee S et al. 2012).

Literature References
PubMed ID Title Journal Year
11149950 LXRs control lipid-inducible expression of the apolipoprotein E gene in macrophages and adipocytes

Laffitte, BA, Repa, JJ, Joseph, SB, Wilpitz, DC, Kast, HR, Mangelsdorf, DJ, Tontonoz, P

Proc. Natl. Acad. Sci. U.S.A. 2001
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