APOE PROMOTER ACTIVITY IS INFLUENCED BY THE APOE 3’UTR

Abstract

Multiple regulatory elements have been described at the APOE locus. These regulatory elements influence gene expression according to cell type. Little is known about the influence of miRNA post-transcriptional regulation at this locus. We have recently described miRNA that are predicted to target APOE as differentially modulated in AD post-mortem brain compared to controls. However, given that the brain tissue is a mix of multiple cell types, we wondered if miRNA targeting of the APOE3’UTR might be cell type specific. The aim of this investigation was to demonstrate that the APOE 3’UTR influences APOE promoter activity according to cell type. Multiple human cell lines were transfected with luciferase reporter constructs containing the APOE promoter and the APOE 3’UTR. APOE promoter activity was influenced by the presence of the APOE 3’UTR according to cell type. These results suggest that a complex regulatory structure at the APOE locus includes an influence by the APOE 3’UTR on the APOE promoter and that this influence is cell type specific.