LuXuRies of Lipid Homeostasis: The Unity of Nuclear Hormone Receptors, Transcription Regulation, and Cholesterol Sensing

LXR and FXR as the regulatory yin and yang of intracellular cholesterol turnover. The RXR–LXR dimer becomes a functional transcription factor when either protomeric constituent binds ligand; the blue circle associated with the LXR in the schematic represents 24(S),25-epoxycholesterol. The dimer therefore binds to its cognate nucleotide sequence (i.e., the LXRE) in the promoter of Cyp7a1, a gene crucial to cholesterol catabolism. Activation of the LXRE by the dimer is enabled through an interaction with LRH-1. As cholesterol is shuttled into bile acid (represented by white circle) production, FXR becomes functional as a transcription factor in the expression of the SHP-encoding gene. SHP binds to LRH-1 and limits the effectiveness of the RXR–LXR dimer. For a list of genes that are activated by LXR, see Table 1.