Identification and Potential Regulatory Properties of Evolutionary Conserved Regions ECRs at the Schizophrenia-Associated MIR137 LocusReportar como inadecuado




Identification and Potential Regulatory Properties of Evolutionary Conserved Regions ECRs at the Schizophrenia-Associated MIR137 Locus - Descarga este documento en PDF. Documentación en PDF para descargar gratis. Disponible también para leer online.

Journal of Molecular Neuroscience

, Volume 60, Issue 2, pp 239–247

First Online: 15 August 2016Received: 15 June 2016Accepted: 01 August 2016

Abstract

Genome-wide association studies GWAS have identified a region at chromosome 1p21.3, containing the microRNA MIR137, to be among the most significant associations for schizophrenia. However, the mechanism by which genetic variation at this locus increases risk of schizophrenia is unknown. Identifying key regulatory regions around MIR137 is crucial to understanding the potential role of this gene in the aetiology of psychiatric disorders. Through alignment of vertebrate genomes, we identified seven non-coding regions at the MIR137 locus with conservation comparable to exons >70 %. Bioinformatic analysis using the Psychiatric Genomics Consortium GWAS dataset for schizophrenia showed five of the ECRs to have genome-wide significant SNPs in or adjacent to their sequence. Analysis of available datasets on chromatin marks and histone modification data showed that three of the ECRs were predicted to be functional in the human brain, and three in development. In vitro analysis of ECR activity using reporter gene assays showed that all seven of the selected ECRs displayed transcriptional regulatory activity in the SH-SY5Y neuroblastoma cell line. This data suggests a regulatory role in the developing and adult brain for these highly conserved regions at the MIR137 schizophrenia-associated locus and further that these domains could act individually or synergistically to regulate levels of MIR137 expression.

KeywordsSchizophrenia microRNA-137 Gene regulation Gene expression Transcription Genetics  Download fulltext PDF



Autor: Olympia Gianfrancesco - Daniel Griffiths - Paul Myers - David A. Collier - Vivien J. Bubb - John P. Quinn

Fuente: https://link.springer.com/article/10.1007/s12031-016-0812-x



DESCARGAR PDF




Documentos relacionados