Functional Analysis of the Promoter of NRXN2α Gene Coding Synaptic Adhesion Molecule

ZHOU Jiahong^#, GUO Yin^#, MENG Shasha, ZHOU Weihui^*

(Department of Pediatric Research Institute, Ministry of Education Key Laboratory of Child Development and Disorders, Chongqing Key Laboratory of Translational Medical Research in Cognitive Development and Learning and Memory Disorders, National Clinical Research Center for Child Health and Disorders, China International Science and Technology Cooperation base of Child development and Critical Disorders, Children’s Hospital of Chongqing Medical University, Chongqing 400014, China)

Abstract:

Neurexins are a family of presynaptic adhesion proteins which play critical roles in overall trans-synaptic signaling network in neurons and circuits. Regulation of gene expression in transcriptional and post-transcriptional levels affects synaptic plasticity and synaptic specificity. To investigate the transcriptional regula-tion of NRXN2α gene, luciferase reporter plasmids containing different regions of 5′ end of NRXN2α gene were constructed and transfected into HEK293 and U-87 MG cells. Then, the promoter activity was determined by the luciferase activity assay of reporter genes. Here, the promoter region of human NRXN2α gene (–911/+60, +1 being the transcription start site) was defined. Then, further study identified the minimal promoter region of NRXN2α gene (–58/+60), which was sufficient to initiate a basal transcription. Moreover, four regions with positive regulatory function (–911/–629, 109/–76, –49/–17, and –17/+60) and one region with negative regulatory function (+146/+238) for transcription of NRXN2α gene were defined. In addition, the typical Inr (initiator) motif in the minimal promoter was characterized. Collectively, for the first time, the promoter region of NRXN2α gene is characterized, and its function in regulating gene expression is analyzed, which lays a foundation for further elucidating its transcriptional regulation mechanism.