The Apolipoprotein(a) Promoter Contains a Retinoid Response Element

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 (RARα) and retinoid X receptor (RXRα) 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 RARα/RXRα 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.