NR1H2,3 binds the NR1H3 gene

Stable Identifier
Homo sapiens
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The gene expression of liver X receptor alpha (LXRα or NR1H3) is autoinduced in a tissue-specific manner ((Whitney KD et al. 2001; Laffitte BA et al. 2001; Li Y et al. 2002). In contrast, NR1H2 (LXRβ) expression is not autoregulated. NR1H3 (LXRα) induction was observed in multiple human cell types including monocyte-derived macrophages, the TPH-1 macrophage cell line and skin fibroblasts in response to NR1H3 and NR1H2 ligands (20(S)-hydroxycholesterol, 22(R)-hydroxycholesterol, 24(S),25-epoxycholesterol, GW3965 or T0901317) (Whitney KD et al. 2001; Laffitte BA et al. 2001; Li Y et al. 2002). No autoregulatory induction of NR1H3 was observed in mouse macrophages (Whitney KD et al. 2001; Laffitte BA et al. 2001; Li Y et al. 2002). There are conflicting data in the literature as to whether this autoregulatory loop is present (Lafitte BA et al. 2001; Li Y et al. 2002) or absent (Whitney DK et al. 2001) in human adipocytes and hepatocytes. T0901317 treatment up-regulated the gene expression of NR1H3 in a dose- and time-dependent fashion in differentiated human THP-1 cells (Li Y et al. 2002). Analysis of the human NR1H3 promoter revealed three LXR response elements (LXREs) (Laffitte BA et al. 2001; Li Y et al. 2002). One exhibited strong affinity for both NR1H2:RXR and NR1H3:RXR (Li Y et al. 2002). Deletions or mutations of this LXRE led to a dramatic loss in the ability of the promoter to respond to T0901317 in transient transfection assays in human hepatocarcinoma Huh-7 cells (Li Y et al. 2002). The other two LXREs are identical to each other, were found within highly conserved Alu repeats, and exhibited selective binding to NR1H3:RXR. In transfections, the first LXRE acted as a strong mediator of both NR1H3 (LXRα) and NR1H2 (LXRβ) activity, whereas the second LXRE acted as a weaker and selective mediator of NR1H3 (LXRα) activity (Li Y et al. 2002).

Literature References
PubMed ID Title Journal Year
11875109 Induction of human liver X receptor alpha gene expression via an autoregulatory loop mechanism

Lala, DS, Xia, C, Bolten, C, Prayaga, SK, Li, S, Li, Y, Bhat, BG, Woodring-Dietz, J

Mol. Endocrinol. 2002
11604492 Autoregulation of the human liver X receptor alpha promoter

Tontonoz, P, Wilpitz, DC, Collins, JL, Walczak, R, Joseph, SB, Pei, L, Laffitte, BA

Mol. Cell. Biol. 2001
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