Glucocerebrosidase gene has an alternative upstream promoter, which has features and expression characteristic of housekeeping genes
Abstract
Database searches have shown that a part of glucocerebrosidase (GBA) transcripts may originate at an alternative upstream promoter (P2) located 2.6 kb upstream of the known (P1) GBA promoter. Luciferase assays confirmed promoter activity of both sites in HepG2 cells: the P1 construct exhibited higher activity of luciferase than the P2.
Serial 5´ deletions of P2 led to changes in reporter activity. Three P2 transcription initiation sites were found by 5´ RACE at positions 347, 380 and 413 bp upstream of the +1 ATG.
The expression stability of transcripts from P2, P1 was studied in 20 human tissues and was higher than that of GAPDH and ACTB, which are commonly used as reference housekeeping genes. The P2 contains an unmethylated CpG island, multiple Sp-1 consensus binding sites and, unlike P1, does not contain a TATA box, features all common to the majority of housekeeping gene promoters.