Abstract
Plasticity-related gene 1 (PRG-1) is a novel player in glutamatergic synaptic transmission, acting by interfering with lysophosphatidic acid (LPA)-dependent signaling pathways. In the central nervous system, PRG-1 expression is restricted to postsynaptic dendrites on glutamatergic neurons. In this study, we describe the promoter architecture of the PRG-1 gene using RNA ligase-mediated rapid amplification of cDNA ends (RLM-Race) and PCR analysis. We found that PRG-1 expression is under the control of a TATA-less promoter with multiple transcription start sites. We demonstrated also that 200-kb genomic environment of the PRG-1 gene is sufficient to mediate cell type-specific expression in a reporter mouse model. Characterization of the PRG-1 promoter resulted in the identification of a 450-bp sequence, mediating ≈40-fold enhancement of transcription in cultured primary neurons compared to controls, and which induced reporter expression in slice cultures in neurons. Recently, the regulation of PRG-1 by the basic helix-loop-helix transcription factor Nex1 (Math2, NeuroD6) was reported. However, our studies in Nex1-null-mice revealed that Nex1-deficiency induces no change in PRG-1 expression and localization. We detected an additional Nex1-independent regulation mechanism that increases PRG-1 expression and mediates neuron-specific expression in an organotypic environment.