Isolation and characterization of the QM promoter.

Abstract

This report describes the isolation, sequencing and preliminary characterization of the first 1 kb of the 5'-regulatory region of the human QM gene. This region and the 5' -half of the transcribed region of the QM gene are enriched for C and G nucleotides with no bias against CpG dinucleotides--indicative of a CpG island. Several consensus GC boxes are present within the sequence. Most are clustered at the distal end, with one site present in the proximal 200 bp of the promoter. Electrophoretic mobility shift experiments and luciferase assays done in insect cells transfected with an Sp1 expression construct suggest that most of these sites can bind Sp1 or a closely related factor. In addition, the promoter is shown to be responsive to cAMP via a response element (CRE) in the proximal promoter. Studies with 5'-end and internal deletion mutants suggest that elements in the distal promoter exert their positive effect through interactions with a proximal element(s). Candidate proximal elements include the proximal GC box and a 43 bp region between a KpnI site (at -182) and a Smal site (at -139).