The role of Sp3 transcription factor in syntaxin 1A gene silencing

Abstract

HPC-1/syntaxin 1A (stx1a) involved in neurotransmission is depressed by YY1 and class1-histone deacetylase in non-neuronal cells/tissue and the decrease of this gene is implicated in neurodevelopmental disorders. To further elucidate the stx1a gene silencing mechanism, in this study, we focused on −210 to −178 common region acting in both neuronal and non-neuronal cells. Electrophoresis mobility shift and supershift assays demonstrated that −210 to −178 region of stx1a core promoter forms DNA-protein complexes including Sp3 and Sp1 in the non-neuronal FRSK cells not expressing stx1a, and that Sp3 and Sp1 bind to −202 to −193 and −190 to −181 regions, which are evenly functioning for stx1a promoter activity. Chromatin immunoprecipitation assays revealed that Sp3 preferentially associates to the stx1a promoter in FRSK cells not expressing stx1a. We also revealed that stx1a transcription in non-neuronal cells is mostly depressed by suppressive forms of Sp3, accounting for the majority. The present study is the first report that stx1a expression is negatively regulated by the suppressive forms of Sp3 transcription factor, which binds to the −202 to −193 and −190 to −181 promoter region in non-neuronal cells.