Genetics
A retinoic acid receptor element is identified in the human CETP gene promoter (Biochem Biophys Res Commun 1999)
Original title: Identification of retinoic acid receptor element in human cholesteryl ester transfer protein gene
Transient transfection of deletion constructs spanning the 3434-bp upstream region of the human CETP gene, linked to a luciferase reporter, into HepG2 cells mapped essential regulatory machinery to the -110/-40 region of the promoter. Stimulation with all-trans retinoic acid produced a hormone response that was drastically reduced when the -165/-110 region was deleted, pointing to a retinoic acid receptor element there. DNase footprinting showed the -165/-134 segment was protected by HepG2 nuclear extract, and gel mobility shift competition with consensus retinoic acid receptor element sequence and purified receptor confirmed -165/-134 as a functional retinoic acid receptor element, identifying a new hormonal pathway that regulates CETP gene transcription.
Original abstract
The transcriptional regulation of the human cholesteryl ester transfer protein (CETP) gene by retinoic acid was investigated by a transient transfection assay. A series of deleted vectors generated from the 5'-upstream region (3434 bp) of the CETP gene linked to the luciferase reporter gene was individually transfected to HepG2 cells. Promoter analyses revealed essential regulatory machinery in the -110/-40 region of the upstream sequence of the human CETP gene. When the cells transfected with the reporter vectors were stimulated with all-trans retinoic acid (tRA), the hormone response was drastically reduced when the -165/-110 region was deleted, thereby suggesting that there may be a retinoic acid receptor element (RARE) in the region. A footprinting analysis showed that the DNA segment at the -165/-134 is protected by the HepG2 nuclear extract. A competition analysis on the gel mobility shift assay using consensus RARE and a purified retinoic acid receptor confirmed the -165/-134 region as being RARE.
Summary written by cetpinhibition.org from the published abstract; figures as published. Page updated 18 August 2026. Methods.