Gale and Ira Drukier Institute for Children's Health

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Long non-coding RNAs discriminate the stages and gene regulatory states of human humoral immune response.

TitleLong non-coding RNAs discriminate the stages and gene regulatory states of human humoral immune response.
Publication TypeJournal Article
Year of Publication2019
AuthorsAgirre X, Meydan C, Jiang Y, Garate L, Doane AS, Li Z, Verma A, Paiva B, Martín-Subero JI, Elemento O, Mason CE, Prosper F, Melnick A
JournalNat Commun
Volume10
Issue1
Pagination821
Date Published2019 02 18
ISSN2041-1723
KeywordsB-Lymphocytes, Enhancer Elements, Genetic, Gene Expression Profiling, Gene Expression Regulation, Gene Regulatory Networks, Genome, Human, Humans, Immunity, Humoral, RNA, RNA, Long Noncoding
Abstract

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.

DOI10.1038/s41467-019-08679-z
Alternate JournalNat Commun
PubMed ID30778059
PubMed Central IDPMC6379396
Grant ListF31 CA220981 / CA / NCI NIH HHS / United States
R35 CA220499 / CA / NCI NIH HHS / United States