znf804a regulates expression of the schizophrenia-associated genes prss16, comt, pde4b, and drd2znf804a调节prss16 schizophrenia-associated基因的表达,comt,pde4b,drd2.pdfVIP

ZNF804a Regulates Expression of the Schizophrenia- Associated Genes PRSS16, COMT, PDE4B, and DRD2 1 1 1,2 Matthew J. Girgenti , Joseph J. LoTurco , Brady J. Maher * 1 Department of Physiology and Neurobiology, University of Connecticut, Storrs, Connecticut, United States of America, 2 Lieber Institute for Brain Development, Johns Hopkins Medical Campus, Baltimore, Maryland, United States of America Abstract ZNF804a was identified by a genome-wide association study (GWAS) in which a single nucleotide polymorphism (SNP rs1344706) in ZNF804a reached genome-wide statistical significance for association with a combined diagnosis of schizophrenia (SZ) and bipolar disorder. Although the molecular function of ZNF804a is unknown, the amino acid sequence is predicted to contain a C2H2-type zinc-finger domain and suggests ZNF804a plays a role in DNA binding and transcription. Here, we confirm that ZNF804a directly contributes to transcriptional control by regulating the expression of several SZ associated genes and directly interacts with chromatin proximal to the promoter regions of PRSS16 and COMT, the two genes we find upregulated by ZNF804a. Using immunochemistry we establish that ZNF804a is localized to the nucleus of rat neural progenitor cells in culture and in vivo. We demonstrate that expression of ZNF804a results in a significant increase in transcript levels of PRSS16 and COMT, relative to GFP transfected controls, and a statistically significant decrease in transcript levels of PDE4B and DRD2. Furthermore, we show using chromatin immunoprecipitation assays (ChIP) that both epitope-tagged and endogenous ZNF804a directly interacts with the promoter regions of PRSS16 and COMT, suggesting a