Structural characterisation of the mouse nuclear oxysterol receptor genes LXRalpha and LXRbeta

Abstract

Oxysterols are important regulatory molecules of diverse biological processes such as cholesterol homeostasis, bile acid synthesis and apoptosis. Recent findings led to the suggestion that some of these functions are mediated by the nuclear receptors LXRalpha and LXRbeta owing to their potential to bind a group of naturally occurring oxysterols as their ligands. In this report, we compare the genomic structure and the promoter regions of the two mouse LXR genes. In addition, we show evidence for the presence of a processed, but truncated LXRbeta pseudogene in the mouse genome. RACE-PCR on mouse liver cDNA demonstrates the presence of more than one defined transcription initiation site for both genes. The LXRalpha and LXRbeta promoter regions are GC-rich and contain a number of putative Sp1 binding sites but lack obvious TATA and CAAT boxes. A database search revealed several sequence motifs in the LXR promoter regions that resemble known transcription factor binding sites. Most striking is the identification of one potential NFkappaB and seven potential Ets-protein binding sites in the LXRbeta promoter, suggesting an important role for this receptor in the haematopoietic/immune system.