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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.

Original publication

DOI

10.1182/blood-2015-11-680843

Type

Journal article

Journal

Blood

Publication Date

18/08/2016

Volume

128

Pages

e10 - e19

Keywords

Animals, B-Lymphocytes, Cell Transformation, Neoplastic, Chromatin, Enhancer Elements, Genetic, Female, Gene Expression Regulation, Genetic Loci, Humans, Lymphocyte Activation, Mice, Inbred C57BL, Open Reading Frames, PAX5 Transcription Factor, Precursor B-Cell Lymphoblastic Leukemia-Lymphoma, Promoter Regions, Genetic, RNA, Long Noncoding