Transcriptional regulation of the α-synuclein gene in human brain tissue

• We identified a new binding site for GATA2 within the 5′-promoter of SNCA.
• zinc finger proteins ZSCAN21 occupy a specific region within human SNCA intron 1.
• zinc finger proteins GATA2 occupy a specific region within human SNCA intron 2.
• No SNPs or mutations were found within the binding sites of ZSCAN21 and GATA2.

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.