Identification and characterization of the human parkin gene promoter

Compound mutations and homozygous loss of function of the parkin gone cause s juvenile and early onset, autosomal recessive parkinsonism. Pathologicall y, the disease is associated with loss of dopaminergic neurons in the subst antia nigra pars compacta and locus ceruleus, usually without Lewy body pat hology. Hemizygous families have been described that may harbor mutations o utside of the open reading frame. The parkin gene promoter has yet to be ch aracterized, and therein, mutations in hemizygous families may plausibly be identified. To identify the promoter of the parkin gene, the transcription start site was defined by a combination of primer extension and 5 ' RACE. Five kilobases of DNA 5 ' to the parkin start codon were directly sequenced from a BAC containing parkin exon 1 and evaluated for promoter motifs. The parkin promoter lacks TATA or CAAT boxes and appears to share homology to the alpha -synuclein promoter. Deletion constructs demonstrated core promot er activity and tissue specific enhancing regions in HEK-293T and SH-SY5Y c ells.