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, researchers from the Francis Crick Institute identified 4516 lncRNAs expressed in 11 different 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 orthologues. Using ChIP-seq they classified 20% of the lncRNAs as either enhancer-associated (eRNA) or promoter-associated (pRNA) RNAs. The researchers 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 catalogue of newly discovered lncRNAs they 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.
Cell-stage specific expression at lncRNA and protein-coding loci
Principal component analysis of regularized log-transformed expression patterns at (A) protein-coding loci and (B) the 4516 lncRNA loci identified in this study. Grey dashed lines indicate groups identified by unsupervised hierarchical clustering. (C) Box plots of specificity of expression of all coding and lncRNA loci separated into quartile bins on the basis of their median expression across all eight B cell stages. Numbers below each quartile indicate the number of lncRNA and protein-coding loci that fall into each category.