GATA transcription factors directly regulate the Parkinson's disease-linked gene α-synuclein Export

@article{citeulike:3124779, abstract = {10.1073/pnas.0802437105 Increased α-synuclein gene () dosage due to locus multiplication causes autosomal dominant Parkinson's disease (PD). Variation in expression may be critical in common, genetically complex PD but the underlying regulatory mechanism is unknown. We show that and the heme metabolism genes , , and form a block of tightly correlated gene expression in 113 samples of human blood, where naturally abounds (validated = 1.6 × 10, 1.8 × 10, and 6.6 × 10). Genetic complementation analysis revealed that these four genes are co-induced by the transcription factor GATA-1. GATA-1 specifically occupies a conserved region within intron-1 and directly induces a 6.9-fold increase in α-synuclein. Endogenous GATA-2 is highly expressed in substantia nigra vulnerable to PD, occupies intron-1, and modulates expression in dopaminergic cells. This critical link between GATA factors and may enable therapies designed to lower α-synuclein production.}, author = {Scherzer, Clemens R. and Grass, Jeffrey A. and Liao, Zhixiang and Pepivani, Imelda and Zheng, Bin and Eklund, Aron C. and Ney, Paul A. and Ng, Juliana and Mcgoldrick, Meghan and Mollenhauer, Brit and Bresnick, Emery H. and Schlossmacher, Michael G.}, citeulike-article-id = {3124779}, citeulike-linkout-0 = {http://dx.doi.org/10.1073/pnas.0802437105}, citeulike-linkout-1 = {http://www.pnas.org/content/105/31/10907.abstract}, citeulike-linkout-2 = {http://www.pnas.org/content/105/31/10907.full.pdf}, citeulike-linkout-3 = {http://view.ncbi.nlm.nih.gov/pubmed/18669654}, citeulike-linkout-4 = {http://www.hubmed.org/display.cgi?uids=18669654}, day = {5}, doi = {10.1073/pnas.0802437105}, journal = {Proceedings of the National Academy of Sciences}, keywords = {er-gata-construct, gata, journalclub, parkinsons-disease, transcription}, number = {31}, pages = {10907--10912}, posted-at = {2008-08-14 20:27:40}, priority = {2}, title = {GATA transcription factors directly regulate the Parkinson's disease-linked gene α-synuclein}, url = {http://dx.doi.org/10.1073/pnas.0802437105}, volume = {105}, year = {2008} }

TY - JOUR ID - citeulike:3124779 L3 - citeulike-article-id:3124779 N2 - 10.1073/pnas.0802437105 Increased α-synuclein gene () dosage due to locus multiplication causes autosomal dominant Parkinson's disease (PD). Variation in expression may be critical in common, genetically complex PD but the underlying regulatory mechanism is unknown. We show that and the heme metabolism genes , , and form a block of tightly correlated gene expression in 113 samples of human blood, where naturally abounds (validated = 1.6 × 10, 1.8 × 10, and 6.6 × 10). Genetic complementation analysis revealed that these four genes are co-induced by the transcription factor GATA-1. GATA-1 specifically occupies a conserved region within intron-1 and directly induces a 6.9-fold increase in α-synuclein. Endogenous GATA-2 is highly expressed in substantia nigra vulnerable to PD, occupies intron-1, and modulates expression in dopaminergic cells. This critical link between GATA factors and may enable therapies designed to lower α-synuclein production. IS - 31 JF - Proceedings of the National Academy of Sciences EP - 10912 TI - GATA transcription factors directly regulate the Parkinson's disease-linked gene α-synuclein VL - 105 SP - 10907 KW - er-gata-construct KW - gata KW - journalclub KW - parkinsons-disease KW - transcription AU - Scherzer, Clemens AU - Grass, Jeffrey AU - Liao, Zhixiang AU - Pepivani, Imelda AU - Zheng, Bin AU - Eklund, Aron AU - Ney, Paul AU - Ng, Juliana AU - Mcgoldrick, Meghan AU - Mollenhauer, Brit AU - Bresnick, Emery AU - Schlossmacher, Michael PY - 2008//05/ UR - http://dx.doi.org/10.1073/pnas.0802437105 ER -