Promoters for the human beta-hexosaminidase genes, HEXA and HEXB.

ABSTRACT Human lysosomal β-hexosaminidases are encoded by two genes, HEXA and HEXB, specifying an α- and a β-subunit, respectively. The subunits dimerize to form β-hexosaminidase A (αβ), β-hexosaminidase B (ββ), and β-hexosaminidase S (αα). This enzyme system has the capacity to degrade a variety of cellular substrates: oligosaccharides, glycosaminoglycans, and glycolipids containing β-linked N-acetylglucosaminyl or N-galactosaminyl residues. Mutations in either the HEXA gene or HEXB gene lead to an accumulation of GM2 ganglioside in neurons, resulting in the severe neurodegenerative disorders termed the GM2 gangliosidoses. To identify the DNA elements responsible for hexosaminidase expression, we ligated the 5′-flanking sequences of both the human and mouse hexosaminidase genes to a chloramphenicol acetyltransferase (CAT) gene. The resulting plasmids were transfected into NIH-3T3 cells and CAT activity was determined as a measure of promoter strength. By 5′ deletion analysis, it was found that essential ...