Long noncoding RNAs in B-cell development and activation
journal contributionposted on 2020-07-15, 08:57 authored by Tiago F Brazão, Jethro S Johnson, Jennifer Müller, Andreas Heger, Chris P Ponting, Victor LJ Tybulewicz
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.
AnimalsB-LymphocytesCell Transformation, NeoplasticChromatinEnhancer Elements, GeneticFemaleGene Expression RegulationGenetic LociHumansLymphocyte ActivationMice, Inbred C57BLOpen Reading FramesPAX5 Transcription FactorPrecursor B-Cell Lymphoblastic Leukemia-LymphomaPromoter Regions, GeneticRNA, Long NoncodingTybulewicz FC001194FC-ackAS-ack1102 Cardiorespiratory Medicine and Haematology1103 Clinical Sciences1114 Paediatrics and Reproductive MedicineImmunology