Identification and characterization of the human parkin gene promoter

Andrew West, Matt Farrer, Leonard Petrucelli, Mark Cookson, Paul Lockhart, John Hardy

Research output: Contribution to journalArticle

32 Scopus citations

Abstract

Compound mutations and homozygous loss of function of the parkin gene causes juvenile and early onset, autosomal recessive parkinsonism. Pathologically, the disease is associated with loss of dopaminergic neurons in the substantia nigra pars compacta and locus ceruleus, usually without Lewy body pathology. Hemizygous families have been described that may harbor mutations outside of the open reading frame. The parkin gene promoter has yet to be characterized, 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 α-synuclein promoter. Deletion constructs demonstrated core promoter activity and tissue specific enhancing regions in HEK-293T and SH-SY5Y cells.

Original languageEnglish (US)
Pages (from-to)1146-1152
Number of pages7
JournalJournal of neurochemistry
Volume78
Issue number5
DOIs
StatePublished - Sep 17 2001

Keywords

  • AR-JP
  • Parkin
  • Parkinson's disease
  • Promoter
  • Transcription regulation

ASJC Scopus subject areas

  • Biochemistry
  • Cellular and Molecular Neuroscience

Fingerprint Dive into the research topics of 'Identification and characterization of the human parkin gene promoter'. Together they form a unique fingerprint.

  • Cite this