title: The selective Alzheimer's disease indicator-1 gene (Seladin-1/DHCR24) is a liver X receptor target gene.
abstract: The nuclear hormone receptors liver X receptor alpha (LXRalpha) and LXRbeta function as physiological receptors for oxidized cholesterol metabolites (oxysterols) and regulate several aspects of cholesterol and lipid metabolism. Seladin-1 was originally identified as a gene whose expression was down-regulated in regions of the brain associated with Alzheimer's disease. Seladin-1 has been demonstrated to be neuroprotective and was later characterized as 3beta-hydroxysterol-Delta24 reductase (DHCR24), a key enzyme in the cholesterologenic pathway. Seladin-1 has also been shown to regulate lipid raft formation. In a whole genome screen for direct LXRalpha target genes, we identified an LXRalpha occupancy site within the second intron of the Seladin-1/DHCR24 gene. We characterized a novel LXR response element within the second intron of this gene that is able to confer LXR-specific ligand responsiveness to reporter gene in both HepG2 and human embryonic kidney 293 cells. Furthermore, we found that Seladin-1/DHCR24 gene expression is significantly decreased in skin isolated from LXRbeta-null mice. Our data suggest that Seladin-1/DHCR24 is an LXR target gene and that LXR may regulate lipid raft formation.
authors.affiliation: Nuclear Receptor Biology Laboratory, Pennington Biomedical Research Center, Louisiana State University System, Baton Rouge, Louisiana, USA.
authors.forename: Yongjun
authors.initials: Y
authors.lastname: Wang
authors.forename: Pamela M
authors.initials: PM
authors.lastname: Rogers
authors.forename: Keith R
authors.initials: KR
authors.lastname: Stayrook
authors.forename: Chen
authors.initials: C
authors.lastname: Su
authors.forename: Gabor
authors.initials: G
authors.lastname: Varga
authors.forename: Qi
authors.initials: Q
authors.lastname: Shen
authors.forename: Sunil
authors.initials: S
authors.lastname: Nagpal
authors.forename: Thomas P
authors.initials: TP
authors.lastname: Burris
mesh_terms: D000544:Alzheimer Disease / Q000235:genetics*; D000818:Animals; D001921:Brain / Q000378:metabolism; D002460:Cell Line; D004268:DNA-Binding Proteins / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D007438:Introns; D000071518:Liver X Receptors; D051379:Mice; D018345:Mice, Knockout; D009419:Nerve Tissue Proteins / Q000235:genetics* / Q000378:metabolism; D057093:Orphan Nuclear Receptors; D044925:Oxidoreductases Acting on CH-CH Group Donors / Q000235:genetics* / Q000378:metabolism; D018160:Receptors, Cytoplasmic and Nuclear / Q000235:genetics* / Q000378:metabolism; D020218:Response Elements; D012867:Skin / Q000378:metabolism
chemical_list: D004268:DNA-Binding Proteins; D000071518:Liver X Receptors; C000605213:NR1H3 protein, human; D009419:Nerve Tissue Proteins; C000605214:Nr1h3 protein, mouse; D057093:Orphan Nuclear Receptors; D018160:Receptors, Cytoplasmic and Nuclear; D044925:Oxidoreductases Acting on CH-CH Group Donors; C499055:DHCR24 protein, human