REGULATION OF THE HUMAN ACID BETA-GLUCOSIDASE PROMOTER IN MULTIPLE CELL-TYPES

Acid beta-glucosidase (beta Glc) is a housekeeping enzyme whose expression Is ubiquitous, but differs greatly according to tissue of origin. Expression of a reporter gene under the control of a 622 bp fragment of the beta Glc promoter correlated roughly with the relative amount of beta Glc mRNA detected in five different cell lines, suggesting that elements within this region play a role in determining differential expression of the beta Glc gene. Experiments using deletion mutants revealed that differential expression of beta Glc is not due to the presence of promoter elements that are active in only certain cell types, but rather due to subtle changes in the magnitude of the effect of the different elements. Strikingly, regulatory elements located upstream of the TATA box are dispensible in several cell types, whereas elements located within exon 1 of the beta Glc gene are essential for reporter gene expression in cultured cells. At least two exon 1 elements regulate mRNA levels, and on; double stranded probe containing exon 1 sequences binds a factor present in extracts from HeLa and glioblastoma cells. Additionally, at least two of the exon 1 elements act in an orientation-independent fashion. Thus, it is likely that at least a subset of the, exon 1 elements act as transcriptional enhancers.