Department of Medicine, Division of Hematology/Oncology, Weill Cornell Medicine, New York, NY, 10021, USA.
Division of Hemato-Oncology, Center for Applied Medical Research (CIMA), University of Navarra, IDISNA, Ciberonc, Pamplona, 31008, Spain.
Nat Commun. 2019 Feb 18;10(1):821. doi: 10.1038/s41467-019-08679-z.
lncRNAs make up a majority of the human transcriptome and have key regulatory functions. Here we perform unbiased de novo annotation of transcripts expressed during the human humoral immune response to find 30% of the human genome transcribed during this process, yet 58% of these transcripts manifest striking differential expression, indicating an lncRNA phylogenetic relationship among cell types that is more robust than that of coding genes. We provide an atlas of lncRNAs in naive and GC B-cells that indicates their partition into ten functionally categories based on chromatin features, DNase hypersensitivity and transcription factor localization, defining lncRNAs classes such as enhancer-RNAs (eRNA), bivalent-lncRNAs, and CTCF-associated, among others. Specifically, eRNAs are transcribed in 8.6% of regular enhancers and 36.5% of super enhancers, and are associated with coding genes that participate in critical immune regulatory pathways, while plasma cells have uniquely high levels of circular-RNAs accounted for by and reflecting the combinatorial clonal state of the Immunoglobulin loci.
lncRNAs 构成了人类转录组的大部分，具有关键的调节功能。在这里，我们进行了无偏的从头转录本注释，以发现人类体液免疫反应过程中表达的转录本，结果发现 30%的人类基因组在此过程中转录，但其中 58%的转录本表现出显著的差异表达，这表明细胞类型之间的 lncRNA 系统发生关系比编码基因更为稳健。我们提供了一个在幼稚和 GC B 细胞中的 lncRNA 图谱，表明它们基于染色质特征、DNase 超敏性和转录因子定位，可分为十个功能类别，定义了 lncRNA 类别，如增强子 RNA（eRNA）、双价 lncRNA 和 CTCF 相关 lncRNA 等。具体来说，eRNA 在 8.6%的常规增强子和 36.5%的超级增强子中被转录，并与参与关键免疫调节途径的编码基因相关，而浆细胞中具有独特的高水平环状 RNA，这反映了免疫球蛋白基因座的组合克隆状态。
