title: Similarity in targets with REST points to neural and glioblastoma related miRNAs.
abstract: There are groups of genes that need coordinated repression in multiple contexts, for example if they code for proteins that work together in a pathway or in a protein complex. Redundancy of biological regulatory networks implies that such coordinated repression might occur at both the pre- and post-transcriptional level, though not necessarily simultaneously or under the same conditions. Here, we propose that such redundancy in the global regulatory network can be detected by the overlap between the putative targets of a transcriptional repressor, as identified by a ChIP-seq experiment, and predicted targets of a microRNA (miRNA). To test this hypothesis, we used publicly available ChIP-seq data of the neural transcriptional repressor RE1 silencing transcription factor (REST) from 15 different cell samples. We found 20 miRNAs, each of which shares a significant amount of predicted targets with REST. The set of predicted associations between these 20 miRNAs and the overlapping REST targets is enriched in known miRNA targets. Many of the detected miRNAs have functions related to neural identity and glioblastoma, which could be expected from their overlap in targets with REST. We propose that the integration of experimentally determined transcription factor binding sites with miRNA-target predictions provides functional information on miRNAs.
authors.affiliation: Max Delbrück Center for Molecular Medicine, Berlin 13125, Germany.
authors.forename: Marie L
authors.initials: ML
authors.lastname: Gebhardt
authors.affiliation: Experimentelle Nephrologie, KIMIII, Universitätsklinikum Jena, Friedrich-Schiller-Universität, Jena 07743, Germany.
authors.forename: Stefanie
authors.initials: S
authors.lastname: Reuter
authors.affiliation: Experimentelle Nephrologie, KIMIII, Universitätsklinikum Jena, Friedrich-Schiller-Universität, Jena 07743, Germany.
authors.forename: Ralf
authors.initials: R
authors.lastname: Mrowka
authors.affiliation: Max Delbrück Center for Molecular Medicine, Berlin 13125, Germany Miguel.andrade@mdc-berlin.de.
authors.forename: Miguel A
authors.initials: MA
authors.lastname: Andrade-Navarro
mesh_terms: D020413:3' Untranslated Regions; D001665:Binding Sites; D045744:Cell Line, Tumor; D047369:Chromatin Immunoprecipitation; D058543:Class Ia Phosphatidylinositol 3-Kinase; D015972:Gene Expression Regulation, Neoplastic; D053263:Gene Regulatory Networks; D005909:Glioblastoma / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D035683:MicroRNAs / Q000235:genetics* / Q000378:metabolism; D008957:Models, Genetic; D009474:Neurons / Q000378:metabolism; D019869:Phosphatidylinositol 3-Kinases / Q000235:genetics / Q000378:metabolism; D011485:Protein Binding; D034622:RNA Interference; D012097:Repressor Proteins / Q000502:physiology*; D000099229:RE1-Silencing Transcription Factor
chemical_list: D020413:3' Untranslated Regions; D058543:Class Ia Phosphatidylinositol 3-Kinase; D035683:MicroRNAs; D019869:Phosphatidylinositol 3-Kinases; D012097:Repressor Proteins; D000099229:RE1-Silencing Transcription Factor; C557400:MIRN448 microRNA, human; C588001:PIK3R1 protein, human
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