Midnolinによる転写調節因子early growth response 1の機能調節

抄録

Parkinson's disease (PD) is an age-associated progressive neurodegenerative disease. Previously, we identified Midnolin (MIDN) as a genetic risk factor for PD. Although MIDN copy number loss increases the risk of PD, the molecular function of MIDN is unknown. To investigate the role of MIDN, we generated Midn knockout (KO) PC-12 cells and performed RNA-Sequencing. Midn KO altered the expression of many genes. While MIDN mainly localizes in the nucleus, MIDN has no DNA binding domain. We, therefore, assumed that MIDN might bind to certain transcription factor(s) (TF(s)) and regulate gene expression. We focused on a TF, early growth response 1 (EGR1) because the promoter region of many genes affected by Midn KO have EGR1 binding regions in common. At first, we confirmed the interaction of MIDN and EGR1 by immunoprecipitation. Then, to examine whether MIDN affects the EGR1-dependent transcription, we developed a reporter plasmid that can monitor EGR1-dependent transcription by measuring luciferase activity. Using the reporter, we confirmed that Midn KO reduced EGR1 transcription activity. These results suggest that the interaction of MIDN and EGR1 promotes EGR1-dependent transcription.