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A significant portion of the genome is transcribed as long noncoding RNAs (lncRNAs), several of which are known to control gene expression. The repertoire and regulation of lncRNAs in disease-relevant tissues, however, has not been systematically explored. We report a comprehensive strand-specific transcriptome map of human pancreatic islets and β cells, and uncover >1100 intergenic and antisense islet-cell lncRNA genes. We find islet lncRNAs that are dynamically regulated and show that they are an integral component of the β cell differentiation and maturation program. We sequenced the mouse islet transcriptome and identify lncRNA orthologs that are regulated like their human counterparts. Depletion of HI-LNC25, a β cell-specific lncRNA, downregulated GLIS3 mRNA, thus exemplifying a gene regulatory function of islet lncRNAs. Finally, selected islet lncRNAs were dysregulated in type 2 diabetes or mapped to genetic loci underlying diabetes susceptibility. These findings reveal a new class of islet-cell genes relevant to β cell programming and diabetes pathophysiology.

Original publication

DOI

10.1016/j.cmet.2012.08.010

Type

Journal article

Journal

Cell Metab

Publication Date

03/10/2012

Volume

16

Pages

435 - 448

Keywords

Animals, Chromatin, DNA-Binding Proteins, Diabetes Mellitus, Type 2, Down-Regulation, Gene Expression Profiling, Genetic Loci, Humans, Insulin-Secreting Cells, Mice, RNA, Long Noncoding, RNA, Messenger, Repressor Proteins, Trans-Activators