title: PRG-1 transcriptional regulation independent from Nex1/Math2-mediated activation.
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.
authors.affiliation: Institute for Microanatomy and Neurobiology, University Medical Center, Johannes Gutenberg University Mainz, 55131, Mainz, Germany.
authors.forename: Beate
authors.initials: B
authors.lastname: Geist
authors.forename: Brita
authors.initials: B
authors.lastname: Vorwerk
authors.forename: Pierluca
authors.initials: P
authors.lastname: Coiro
authors.forename: Olaf
authors.initials: O
authors.lastname: Ninnemann
authors.forename: Robert
authors.initials: R
authors.lastname: Nitsch
mesh_terms: D000818:Animals; D051792:Basic Helix-Loop-Helix Proteins / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D002478:Cells, Cultured; D005786:Gene Expression Regulation; D051379:Mice; D008810:Mice, Inbred C57BL; D009419:Nerve Tissue Proteins / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D009474:Neurons / Q000378:metabolism; D011401:Promoter Regions, Genetic; D011509:Proteoglycans / Q000235:genetics* / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D024363:Transcription Initiation Site; D015533:Transcriptional Activation; D033921:Vesicular Transport Proteins / Q000235:genetics* / Q000378:metabolism*
chemical_list: D051792:Basic Helix-Loop-Helix Proteins; D009419:Nerve Tissue Proteins; D011509:Proteoglycans; D033921:Vesicular Transport Proteins; C110701:Neurod6 protein, mouse; C075430:serglycin