NR1H2,3 binds the NR1H3 gene

Stable Identifier
Reaction [binding]
Homo sapiens
Locations in the PathwayBrowser
SVG |   | PPTX  | SBGN
Click the image above or here to open this reaction in the Pathway Browser
The layout of this reaction may differ from that in the pathway view due to the constraints in pathway layout

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
Cite Us!