Figure 5.

The apoE ME.1 and ME.2 enhancers are direct targets for binding LXR/RXR heterodimers. (A) Genomic structure of the apoE locus and location of potential LXREs. ApoE LXRES are aligned with a known LXRE from the cholesterol-7-α-hydroxylase gene (CYP7α LXRE) and an idealized LXRE (β-DR-4). Also shown is the sequence of a mutant ME LXRE (ME MUT LXRE) used in C and D. (B) Direct binding of LXRα/RXRα and LXRβ/RXRα to a low-affinity LXRE present in the proximal promoter and a high-affinity site conserved in both ME.1 and ME.2. Gel mobility-shift assays were performed with the use of in vitro translated receptors as described in Materials and Methods. (C and D) Sequence-specific competition for LXRα/RXRα (C) and LXRβ/RXRα (D) binding to the ME LXRE.