GSE114816
Long non-coding RNAs discriminate the stages and gene regulatory states of the human humoral immune response (RNA-Seq)
Long non-coding RNAs (lncRNAs) make up a vast majority of the human transcriptome and have key regulatory functions. We performed unbiased de novo annotation of transcripts expressed during the humoral immune response in humans. Remarkably, 30% of the total human genome is transcribed during this process, and yet 58% of these transcripts manifest striking differential expression indicating phylogenetic relationships among cell types that is even more robust than coding genes. We provide a regulatory atlas of lncRNAs in naïve B and GC B-cells that indicates their partition into ten functionally distinct categories based on chromatin features including H3K4me1, H3K4me2, H3K4me3, H3K27ac, H3K27me3, DNase hypersensitivity, CTCF, EP300, CREBBP, MED1, BRD4, FOXO1 and FOXP1 localization. This procedure defined lncRNAs classes such as enhancer RNA (eRNA), bivalent lncRNA, and CTCF associated, among others. eRNAs are transcribed in 8.6% of regular enhancers and 36.5% of super enhancers, associated with coding genes that participate in critical immune regulatory pathways. Plasma cells uniquely featured high levels of circular RNAs accounted for by and reflecting the combinatorial clonal state of the Immunoglobulin loci. Overall design: Detection and funtional study of novel and annotated expressed lncRNAs during human humoral immune response