title: Promoter-like sequences regulating transcriptional activity in neurexin and neuroligin genes.
abstract: Synapse function requires the cell-adhesion molecules neurexins (Nrxn) and neuroligins (Nlgn). Although these molecules are essential for neurotransmission and prefer distinct isoform combinations for interaction, little is known about their transcriptional regulation. Here, we started to explore this important aspect because expression of Nrxn1-3 and Nlgn1-3 genes is altered in mice lacking the transcriptional regulator methyl-CpG-binding protein2 (MeCP2). Since MeCP2 can bind to methylated CpG-dinucleotides and Nrxn/Nlgn contain CpG-islands, we tested genomic sequences for transcriptional activity in reporter gene assays. We found that their influence on transcription are differentially activating or inhibiting. As we observed an activity difference between heterologous and neuronal cell lines for distinct Nrxn1 and Nlgn2 sequences, we dissected their putative promoter regions. In both genes, we identify regions in exon1 that can induce transcription, in addition to the alternative transcriptional start points in exon2. While the 5'-regions of Nrxn1 and Nlgn2 contain two CpG-rich elements that show distinct methylation frequency and binding to MeCP2, other regions may act independently of this transcriptional regulator. These data provide first insights into regulatory sequences of Nrxn and Nlgn genes that may represent an important aspect of their function at synapses in health and disease.
authors.affiliation: Institute of Anatomy and Molecular Neurobiology, Westfälische Wilhelms-University, Münster, Germany.
authors.forename: Fabian
authors.initials: F
authors.lastname: Runkel
authors.forename: Astrid
authors.initials: A
authors.lastname: Rohlmann
authors.forename: Carsten
authors.initials: C
authors.lastname: Reissner
authors.forename: Stefan-Martin
authors.initials: SM
authors.lastname: Brand
authors.forename: Markus
authors.initials: M
authors.lastname: Missler
mesh_terms: D000818:Animals; D015153:Blotting, Western; D002135:Calcium-Binding Proteins; D015816:Cell Adhesion Molecules, Neuronal / Q000235:genetics*; D047369:Chromatin Immunoprecipitation; D005786:Gene Expression Regulation / Q000235:genetics / Q000502:physiology; D008156:Luciferases / Q000235:genetics; D008565:Membrane Proteins / Q000235:genetics*; D051783:Methyl-CpG-Binding Protein 2 / Q000235:genetics; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009419:Nerve Tissue Proteins / Q000235:genetics*; D019006:Neural Cell Adhesion Molecules / Q000235:genetics*; D016716:PC12 Cells; D016133:Polymerase Chain Reaction; D011401:Promoter Regions, Genetic / Q000235:genetics*; D051381:Rats
chemical_list: D002135:Calcium-Binding Proteins; D015816:Cell Adhesion Molecules, Neuronal; C497393:Mecp2 protein, mouse; D008565:Membrane Proteins; D051783:Methyl-CpG-Binding Protein 2; D009419:Nerve Tissue Proteins; D019006:Neural Cell Adhesion Molecules; C527193:Nrxn1 protein, mouse; C583456:neurexin 3, mouse; C093175:neurexin II; C093438:neuroligin 1; C098003:neuroligin 2; C098004:neuroligin 3; D008156:Luciferases
keywords: CpG island; MeCP2; neurexin; neuroligin; promoter; transcriptional activity