title: Long noncoding RNAs in B-cell development and activation.
abstract: Long noncoding RNAs (lncRNAs) are potentially important regulators of cell differentiation and development, but little is known about their roles in B lymphocytes. Using RNA-seq and de novo transcript assembly, we identified 4516 lncRNAs expressed in 11 stages of B-cell development and activation. Most of these lncRNAs have not been previously detected, even in the closely related T-cell lineage. Comparison with lncRNAs previously described in human B cells identified 185 mouse lncRNAs that have human orthologs. Using chromatin immunoprecipitation-seq, we classified 20% of the lncRNAs as either enhancer-associated (eRNA) or promoter-associated RNAs. We identified 126 eRNAs whose expression closely correlated with the nearest coding gene, thereby indicating the likely location of numerous enhancers active in the B-cell lineage. Furthermore, using this catalog of newly discovered lncRNAs, we show that PAX5, a transcription factor required to specify the B-cell lineage, bound to and regulated the expression of 109 lncRNAs in pro-B and mature B cells and 184 lncRNAs in acute lymphoblastic leukemia.
authors.affiliation: The Francis Crick Institute, London, United Kingdom;
authors.forename: Tiago F
authors.identifier: 0000-0002-0760-4873
authors.initials: TF
authors.lastname: Brazão
authors.affiliation: Medical Research Council (MRC) Computational Genomics Analysis and Training Centre, MRC Functional Genomics Unit, Department of Physiology Anatomy and Genetics, University of Oxford, Oxford, United Kingdom; and.
authors.forename: Jethro S
authors.identifier: 0000-0001-9155-054X
authors.initials: JS
authors.lastname: Johnson
authors.affiliation: The Francis Crick Institute, London, United Kingdom;
authors.forename: Jennifer
authors.initials: J
authors.lastname: Müller
authors.affiliation: Medical Research Council (MRC) Computational Genomics Analysis and Training Centre, MRC Functional Genomics Unit, Department of Physiology Anatomy and Genetics, University of Oxford, Oxford, United Kingdom; and.
authors.forename: Andreas
authors.identifier: 0000-0001-7720-0447
authors.initials: A
authors.lastname: Heger
authors.affiliation: Medical Research Council (MRC) Computational Genomics Analysis and Training Centre, MRC Functional Genomics Unit, Department of Physiology Anatomy and Genetics, University of Oxford, Oxford, United Kingdom; and.
authors.forename: Chris P
authors.identifier: 0000-0003-0202-7816
authors.initials: CP
authors.lastname: Ponting
authors.affiliation: The Francis Crick Institute, London, United Kingdom; Imperial College, London, United Kingdom.
authors.forename: Victor L J
authors.identifier: 0000-0003-2439-0798
authors.initials: VL
authors.lastname: Tybulewicz
mesh_terms: D000818:Animals; D001402:B-Lymphocytes / Q000276:immunology*; D002471:Cell Transformation, Neoplastic / Q000235:genetics / Q000473:pathology; D002843:Chromatin / Q000378:metabolism; D004742:Enhancer Elements, Genetic / Q000235:genetics; D005260:Female; D005786:Gene Expression Regulation; D056426:Genetic Loci; D006801:Humans; D008213:Lymphocyte Activation / Q000235:genetics*; D008810:Mice, Inbred C57BL; D016366:Open Reading Frames / Q000235:genetics; D051757:PAX5 Transcription Factor / Q000378:metabolism; D015452:Precursor B-Cell Lymphoblastic Leukemia-Lymphoma / Q000235:genetics / Q000473:pathology; D011401:Promoter Regions, Genetic / Q000235:genetics; D062085:RNA, Long Noncoding / Q000235:genetics / Q000378:metabolism*
chemical_list: D002843:Chromatin; D051757:PAX5 Transcription Factor; D062085:RNA, Long Noncoding