Yy1 regulates Senp1 contributing to AMPA receptor GluR1 expression following neuronal depolarization

• DOI: 10.1186/s12929-019-0582-1
• Publication Date: 2019-10-20T02:09:38Z
• Authors: Tao Wu; Mary E. Donohoe
• Keywords: Neurons; 0301 basic medicine; Research; R; Nuclear Proteins; Embryo, Mammalian; Yy1; GluR1; Mice, Inbred C57BL; Cysteine Endopeptidases; 03 medical and health sciences; Neuronal membrane depolarization; Gene Expression Regulation; Brd4; Medicine; Animals; Receptors, AMPA; Senp1; Phosphorylation; YY1 Transcription Factor; Transcription Factors

Abstract Background Neuronal activity-induced changes in gene expression patterns are important mediators of neuronal plasticity. Many genes can be activated or inactivated response to depolarization. Mechanisms that activate transcription well established, but activity-dependent mechanisms silence less understood. It is also not clear what the significance inhibiting these during activity. Methods Quantitative Real Time-PCR, western blot and immunofluorescence staining were performed examine Senp1 GluR1 mouse cortical neurons. The alterations Yy1 phosphorylation upon depolarization interaction with Brd4 studied by protein co-immunoprecipitation. regulators identified phosphatase inhibitors. Chromatin immunoprecipitation, vitro DNA binding assay, luciferase assay knockdown experiments used validate roles its as regulating expression. Results We report deactivates SUMO protease , an component synaptic transmission, scaling, plasticity, through Yy1. In un-stimulated neurons, a Yy1-Brd4 factor complex assembled on promoter. Upon membrane depolarization, however, dephosphorylated evicted from promoter, reducing levels. Both promote AMPA receptor subunit GluR1, pivotal learning memory. Conclusions These results reveal axis Yy1/Brd4-Senp1 which regulates This implicates regulation mechanism silencing