title: Transcriptional regulation of the α-synuclein gene in human brain tissue.
abstract: The transcriptional regulation of the gene encoding α-synuclein (SNCA) is thought to play a critical role in the pathogenesis of Parkinson's disease (PD), as common genetic variability in this gene is associated with an elevated risk of developing PD. However, the relevant mechanisms are still poorly understood. So far, only few proteins have been identified as transcription factors (TFs) of SNCA in cellular models. Here we show that two of these TFs bind to the DNA in human brain tissue: the zinc finger protein ZSCAN21 occupies a region within SNCA intron 1, as described before, while GATA2 occupies a specific region within intron 2, where we have identified a new binding site within the complex structure of the 5'-promoter region of SNCA. Electrophoretic mobility shift assays confirmed these binding sites. Genetic investigations revealed no polymorphisms or mutations within these sites. A better understanding of TF-DNA interactions within SNCA may allow to develop novel therapies designed to reduce α-synuclein levels.
authors.affiliation: Hertie Institute for Clinical Brain Research, Department of Neurodegenerative diseases, University of Tübingen, Tübingen, Germany. Electronic address: brenner.steffen@googlemail.com.
authors.forename: Steffen
authors.initials: S
authors.lastname: Brenner
authors.affiliation: Hertie Institute for Clinical Brain Research, Department of Neurodegenerative diseases, University of Tübingen, Tübingen, Germany; German Center for Neurodegenerative diseases (DZNE), Tübingen, Germany.
authors.forename: Christophe
authors.initials: C
authors.lastname: Wersinger
authors.affiliation: Hertie Institute for Clinical Brain Research, Department of Neurodegenerative diseases, University of Tübingen, Tübingen, Germany; German Center for Neurodegenerative diseases (DZNE), Tübingen, Germany.
authors.forename: Thomas
authors.initials: T
authors.lastname: Gasser
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001665:Binding Sites; D001921:Brain / Q000378:metabolism*; D022782:CCAAT-Enhancer-Binding Protein-beta / Q000235:genetics / Q000378:metabolism; D016022:Case-Control Studies; D005260:Female; D050989:GATA2 Transcription Factor / Q000235:genetics / Q000378:metabolism; D005786:Gene Expression Regulation; D006801:Humans; D007438:Introns; D051741:Kruppel-Like Transcription Factors / Q000235:genetics / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D010300:Parkinson Disease / Q000378:metabolism; D011110:Polymorphism, Genetic; D011401:Promoter Regions, Genetic; D015534:Trans-Activators; D014158:Transcription, Genetic; D016335:Zinc Fingers; D051844:alpha-Synuclein / Q000235:genetics / Q000378:metabolism*
chemical_list: D022782:CCAAT-Enhancer-Binding Protein-beta; C545012:CEBPB protein, human; D050989:GATA2 Transcription Factor; C494711:GATA2 protein, human; D051741:Kruppel-Like Transcription Factors; D015534:Trans-Activators; C510393:ZSCAN21 protein, human; D051844:alpha-Synuclein
keywords: GATA2; Gene expression; Parkinson’s disease; SNP; ZSCAN21; α-Synuclein