title: Thyroid hormone receptor and liver X receptor competitively up-regulate human selective Alzheimer's disease indicator-1 gene expression at the transcriptional levels.
abstract: Selective Alzheimer's disease (AD) indicator-1 (Seladin-1) gene has been identified as a gene, whose expression is down-regulated in the vulnerable region in the brain of AD patients. Thyroid hormone (TH) is important to maintain the function of central nervous system and TH receptor (TR) is known to crosstalk with liver X receptor (LXR) on the lipid metabolism-related gene promoter. Recently, we have demonstrated that TR-β up-regulates the mouse Seladin-1 gene promoter at the transcriptional levels and LXR-α compensates the promoter activation only when the thyroid function is insufficient. In the current study, we have identified that TH and an LXR artificial agonist, TO901317 (TO) activated the human Seladin-1 promoter (-1024/+57 base pair (bp)) including consensus TH response element (TRE) half site (site A: -381 to -375 bp), and the site A mutation deteriorated the activation by TH and TO. Both TR-β and LXR-α heterodimerize with retinoid X receptor (RXR)-α on the site A, and chromatin immunoprecipitation (ChIP) assay revealed that TR-β, LXR-α and RXR-α are recruited to the site A. Moreover, TR-β and LXR-α functionally compete for the promoter activation in CV1 cells. Taken together, we concluded that TR-β and LXR-α competitively up-regulate the human Seladin-1 promoter, sharing the same response element, site A.
authors: Department of Medicine and Molecular Science, Gunma University Graduate School of Medicine, Maebashi, Gunma, Japan.
authors: Emi
authors: E
authors: Ishida
authors: Koshi
authors: K
authors: Hashimoto
authors: Shuichi
authors: S
authors: Okada
authors: Tetsurou
authors: T
authors: Satoh
authors: Masanobu
authors: M
authors: Yamada
authors: Masatomo
authors: M
authors: Mori
mesh_terms: D000544:Alzheimer Disease / Q000235:genetics*; D001483:Base Sequence; D001667:Binding, Competitive; D045744:Cell Line, Tumor; D016384:Consensus Sequence; D005786:Gene Expression Regulation; D006801:Humans; D006845:Hydrocarbons, Fluorinated / Q000494:pharmacology; D000071518:Liver X Receptors; D009419:Nerve Tissue Proteins / Q000235:genetics*; D057093:Orphan Nuclear Receptors / Q000819:agonists / Q000378:metabolism*; D044925:Oxidoreductases Acting on CH-CH Group Donors / Q000235:genetics*; D020218:Response Elements / Q000187:drug effects / Q000235:genetics; D013449:Sulfonamides / Q000494:pharmacology; D037042:Thyroid Hormone Receptors beta / Q000819:agonists / Q000378:metabolism*; D014158:Transcription, Genetic; D015854:Up-Regulation; D005466:Fluorocarbons; D000096926:Benzenesulfonamides
chemical_list: D006845:Hydrocarbons, Fluorinated; D000071518:Liver X Receptors; D009419:Nerve Tissue Proteins; D057093:Orphan Nuclear Receptors; D044925:Oxidoreductases Acting on CH-CH Group Donors; D013449:Sulfonamides; D037042:Thyroid Hormone Receptors beta; C000605213:NR1H3 protein, human; C000605214:Nr1h3 protein, mouse; C423915:T0901317; D005466:Fluorocarbons; D000096926:Benzenesulfonamides; C499055:DHCR24 protein, human