Identification of factors regulating the expression of the human glucocerebrosidase gene

Gaucher disease, the most prevalent sphingolipid disorder, is characterized by an accumulation of sphingolipids mainly in cells of the reticuloendothelial cells, and is due to decreased activity of the lysosomal enzyme glucocerebrosidase (GCase). The corresponding gene is expressed differentially, namely in different cell types there are different GCase steady-state mRNA levels. Electrophoretic mobility shift assays, DNase footprinting and chloramphenicol acetyl transferase assays were employed in order to unravel some of the transcription factors responsible for the differential expression of the glucocerebrosidase (gcs) gene. The results indicate that OCTA binding protein, AP-1, PEA3 and a CAAT binding protein participate in regulating the expression of the gcs gene. The availability of the transcription factors seems to control the level of transcription of the gcs gene.