title: The apolipoprotein(a) promoter contains a retinoid response element.
abstract: Retinoids were previously shown to lower apolipoprotein(a) [apo(a)] mRNA levels, suggesting that the apo(a) promoter contains a retinoid response element (RRE). Scanning the apo(a) promoter for sequences related to the consensus RRE half-site (5'-PuG(G/T)TCA-3') uncovered four sites that could potentially function as RREs at -2915, -1875, -1036, and -407. The activity of these sites was assessed by their ability to compete with a very strong consensus DR5 RRE for binding to retinoic acid receptor (RARalpha) and retinoid X receptor (RXRalpha) heterodimers using electrophoretic mobility-shift assays. Only the -1036 site (5'-TGACCTTGTGATCC-'3) was an effective competitor of the DR5 RRE; therefore, it was designated as apo(a) RRE. Apo(a) RRE competed with DR5 RRE for RARalpha/RXRalpha binding with 1/10 the affinity of DR5 RRE, while a scrambled apo(a) RRE was inactive. These results suggested that apo(a) RRE is a potential candidate for mediating the effect retinoids have on apo(a) mRNA expression.
authors.affiliation: Department of Vascular and Cardiac Diseases, Division of Warner-Lambert Company, Parke-Davis Pharmaceutical Research, Ann Arbor, Michigan, 48105, USA. ramharr@aa.wl.com
authors.forename: R
authors.initials: R
authors.lastname: Ramharack
authors.forename: R J
authors.initials: RJ
authors.lastname: Wyborski
authors.forename: M A
authors.initials: MA
authors.lastname: Spahr
mesh_terms: D001667:Binding, Competitive; D016384:Consensus Sequence / Q000235:genetics; D004268:DNA-Binding Proteins / Q000032:analysis; D019281:Dimerization; D005786:Gene Expression Regulation / Q000235:genetics; D017270:Lipoprotein(a) / Q000235:genetics*; D011401:Promoter Regions, Genetic / Q000235:genetics*; D012333:RNA, Messenger / Q000378:metabolism; D018168:Receptors, Retinoic Acid / Q000378:metabolism; D047488:Retinoid X Receptors; D012176:Retinoids / Q000378:metabolism*; D014157:Transcription Factors / Q000378:metabolism
chemical_list: D004268:DNA-Binding Proteins; D017270:Lipoprotein(a); D012333:RNA, Messenger; D018168:Receptors, Retinoic Acid; D047488:Retinoid X Receptors; D012176:Retinoids; D014157:Transcription Factors