title: Long noncoding RNAs as a novel component of the Myc transcriptional network.
abstract: Myc is a well-known transcription factor with important roles in cell cycle, apoptosis, and cellular transformation. Long noncoding RNAs (lncRNAs) have recently emerged as an important class of regulatory RNAs. Here, we show that lncRNAs are a main component of the Myc-regulated transcriptional program using the P493-6 tetracycline-repressible myc model. We demonstrate that both Myc-induced mRNAs and lncRNAs are significantly enriched for Myc binding sites. In contrast to Myc-repressed mRNAs, Myc-repressed lncRNAs are significantly enriched for Myc binding sites. Subcellular localization analysis revealed that compared to mRNAs, lncRNAs more often have a specific subcellular localization with a markedly higher percentage of nuclear enrichment within the Myc-repressed lncRNA set. Parallel analysis of differentially expressed lncRNAs and mRNAs identified 105 juxtaposed lncRNA-mRNA pairs, indicative for regulation in cis. To support the potential relevance of the Myc-regulated lncRNAs in cellular transformation, we analyzed their expression in primary Myc-high and Myc-low B-cell lymphomas. In total, 54% of the lncRNAs differentially expressed between the lymphoma subsets were identified as Myc-regulated in P493-6 cells. This study is the first to show that lncRNAs are an important factor within the Myc-regulated transcriptional program and indicates a marked difference between Myc-repressed lncRNAs and mRNAs.
authors.affiliation: *Department of Pathology and Medical Biology and Department of Genetics, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.
authors.forename: Melanie
authors.initials: M
authors.lastname: Winkle
authors.affiliation: *Department of Pathology and Medical Biology and Department of Genetics, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.
authors.forename: Anke
authors.initials: A
authors.lastname: van den Berg
authors.affiliation: *Department of Pathology and Medical Biology and Department of Genetics, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.
authors.forename: Masoumeh
authors.initials: M
authors.lastname: Tayari
authors.affiliation: *Department of Pathology and Medical Biology and Department of Genetics, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.
authors.forename: Jantine
authors.initials: J
authors.lastname: Sietzema
authors.affiliation: *Department of Pathology and Medical Biology and Department of Genetics, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.
authors.forename: Martijn
authors.initials: M
authors.lastname: Terpstra
authors.affiliation: *Department of Pathology and Medical Biology and Department of Genetics, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.
authors.forename: Gertrud
authors.initials: G
authors.lastname: Kortman
authors.affiliation: *Department of Pathology and Medical Biology and Department of Genetics, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.
authors.forename: Debora
authors.initials: D
authors.lastname: de Jong
authors.affiliation: *Department of Pathology and Medical Biology and Department of Genetics, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.
authors.forename: Lydia
authors.initials: L
authors.lastname: Visser
authors.affiliation: *Department of Pathology and Medical Biology and Department of Genetics, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.
authors.forename: Arjan
authors.initials: A
authors.lastname: Diepstra
authors.affiliation: *Department of Pathology and Medical Biology and Department of Genetics, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.
authors.forename: Klaas
authors.initials: K
authors.lastname: Kok
authors.affiliation: *Department of Pathology and Medical Biology and Department of Genetics, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands j.l.kluiver@umcg.nl.
authors.forename: Joost
authors.initials: J
authors.lastname: Kluiver
mesh_terms: D015153:Blotting, Western; D002460:Cell Line; D045744:Cell Line, Tumor; D002467:Cell Nucleus / Q000235:genetics / Q000378:metabolism; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D053263:Gene Regulatory Networks / Q000235:genetics*; D006801:Humans; D016393:Lymphoma, B-Cell / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D020411:Oligonucleotide Array Sequence Analysis; D016271:Proto-Oncogene Proteins c-myc / Q000235:genetics* / Q000378:metabolism; D034622:RNA Interference; D062085:RNA, Long Noncoding / Q000235:genetics* / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: C489427:MYC protein, human; D016271:Proto-Oncogene Proteins c-myc; D062085:RNA, Long Noncoding; D012333:RNA, Messenger
keywords: B-cell lymphoma; cancer; regulation