Divergent transcription of long noncoding RNA/mRNA gene pairs in embryonic stem cells

Many long noncoding RNA (lncRNA) species have been identified in mammalian cells, but the genomic origin and regulation of these molecules in individual cell types is poorly understood. We have generated catalogs of lncRNA species expressed in human and murine embryonic stem cells and mapped their genomic origin. A surprisingly large fraction of these transcripts (>60%) originate from divergent transcription at promoters of active protein-coding genes. The divergently transcribed lncRNA/mRNA gene pairs exhibit coordinated changes in transcription when embryonic stem cells are differentiated into endoderm. Our results reveal that transcription of most lncRNA genes is coordinated with transcription of protein-coding genes.

[1]  John T. Lis,et al.  Promoter-proximal pausing of RNA polymerase II: emerging roles in metazoans , 2012, Nature Reviews Genetics.

[2]  David G. Knowles,et al.  The GENCODE v7 catalog of human long noncoding RNAs: Analysis of their gene structure, evolution, and expression , 2012, Genome research.

[3]  Nadav S. Bar,et al.  Landscape of transcription in human cells , 2012, Nature.

[4]  D. Bartel,et al.  Conserved Function of lincRNAs in Vertebrate Embryonic Development despite Rapid Sequence Evolution , 2011, Cell.

[5]  M. Esteller Non-coding RNAs in human disease , 2011, Nature Reviews Genetics.

[6]  O. Abdel-Wahab,et al.  Faculty Opinions recommendation of lincRNAs act in the circuitry controlling pluripotency and differentiation. , 2011 .

[7]  Ahsan Huda,et al.  Faculty Opinions recommendation of Mapping and analysis of chromatin state dynamics in nine human cell types. , 2011 .

[8]  David A. Orlando,et al.  Master Transcription Factors Determine Cell-Type-Specific Responses to TGF-β Signaling , 2011, Cell.

[9]  J. Rinn,et al.  Integrative annotation of human large intergenic noncoding RNAs reveals global properties and specific subclasses. , 2011, Genes & development.

[10]  Albert E. Almada,et al.  Antisense RNA polymerase II divergent transcripts are P-TEFb dependent and substrates for the RNA exosome , 2011, Proceedings of the National Academy of Sciences.

[11]  Howard Y. Chang,et al.  Extensive and coordinated transcription of noncoding RNAs within cell cycle promoters , 2011, Nature Genetics.

[12]  Leighton J. Core,et al.  Regulating RNA polymerase pausing and transcription elongation in embryonic stem cells. , 2011, Genes & development.

[13]  Richard A Young,et al.  Control of the Embryonic Stem Cell State , 2011, Cell.

[14]  Sibum Sung,et al.  Vernalization-Mediated Epigenetic Silencing by a Long Intronic Noncoding RNA , 2011, Science.

[15]  R. Young,et al.  Histone H3K27ac separates active from poised enhancers and predicts developmental state , 2010, Proceedings of the National Academy of Sciences.

[16]  Leonard Lipovich,et al.  Genome-wide computational identification and manual annotation of human long noncoding RNA genes. , 2010, RNA.

[17]  Lee E. Edsall,et al.  Distinct epigenomic landscapes of pluripotent and lineage-committed human cells. , 2010, Cell stem cell.

[18]  J. Rinn,et al.  Ab initio reconstruction of transcriptomes of pluripotent and lineage committed cells reveals gene structures of thousands of lincRNAs , 2010, Nature Biotechnology.

[19]  Christopher B. Burge,et al.  c-Myc Regulates Transcriptional Pause Release , 2010, Cell.

[20]  C. Ponting,et al.  Genomic and Transcriptional Co-Localization of Protein-Coding and Long Non-Coding RNA Pairs in the Developing Brain , 2009, PLoS genetics.

[21]  J. Rinn,et al.  Many human large intergenic noncoding RNAs associate with chromatin-modifying complexes and affect gene expression , 2009, Proceedings of the National Academy of Sciences.

[22]  Michael F. Lin,et al.  Chromatin signature reveals over a thousand highly conserved large non-coding RNAs in mammals , 2009, Nature.

[23]  Gene W. Yeo,et al.  Divergent Transcription from Active Promoters , 2008, Science.

[24]  M. Schierup,et al.  RNA Exosome Depletion Reveals Transcription Upstream of Active Human Promoters , 2008, Science.

[25]  Leighton J. Core,et al.  Nascent RNA Sequencing Reveals Widespread Pausing and Divergent Initiation at Human Promoters , 2008, Science.

[26]  Jennifer A. Erwin,et al.  Polycomb Proteins Targeted by a Short Repeat RNA to the Mouse X Chromosome , 2008, Science.

[27]  J. Komorowski,et al.  Kcnq1ot1 antisense noncoding RNA mediates lineage-specific transcriptional silencing through chromatin-level regulation. , 2008, Molecular cell.

[28]  Eric T. Wang,et al.  Alternative Isoform Regulation in Human Tissue Transcriptomes , 2008, Nature.

[29]  Megan F. Cole,et al.  Connecting microRNA Genes to the Core Transcriptional Regulatory Circuitry of Embryonic Stem Cells , 2008, Cell.

[30]  Paulo P. Amaral,et al.  Long noncoding RNAs in mouse embryonic stem cell pluripotency and differentiation. , 2008, Genome research.

[31]  S. Sunkin,et al.  Specific expression of long noncoding RNAs in the mouse brain , 2008, Proceedings of the National Academy of Sciences.

[32]  A. Feinberg,et al.  Epigenetic silencing of tumour suppressor gene p15 by its antisense RNA , 2008, Nature.

[33]  R. Jaenisch,et al.  A Chromatin Landmark and Transcription Initiation at Most Promoters in Human Cells , 2007, Cell.

[34]  Yong Zhang,et al.  CPC: assess the protein-coding potential of transcripts using sequence features and support vector machine , 2007, Nucleic Acids Res..

[35]  P. Stadler,et al.  RNA Maps Reveal New RNA Classes and a Possible Function for Pervasive Transcription , 2007, Science.

[36]  Howard Y. Chang,et al.  Anatomic Demarcation by Positional Variation in Fibroblast Gene Expression Programs , 2006, PLoS genetics.

[37]  Brian S. Clark,et al.  The Evf-2 noncoding RNA is transcribed from the Dlx-5/6 ultraconserved region and functions as a Dlx-2 transcriptional coactivator. , 2006, Genes & development.

[38]  Megan F. Cole,et al.  Core Transcriptional Regulatory Circuitry in Human Embryonic Stem Cells , 2005, Cell.

[39]  S. Salzberg,et al.  The Transcriptional Landscape of the Mammalian Genome , 2005, Science.

[40]  Dawood B. Dudekula,et al.  Genome-wide assembly and analysis of alternative transcripts in mouse. , 2005, Genome research.

[41]  C. Cepko,et al.  The Noncoding RNA Taurine Upregulated Gene 1 Is Required for Differentiation of the Murine Retina , 2005, Current Biology.

[42]  Tatiana Tatusova,et al.  NCBI Reference Sequence (RefSeq): a curated non-redundant sequence database of genomes, transcripts and proteins , 2004, Nucleic Acids Res..

[43]  Charles Kooperberg,et al.  The histone modification pattern of active genes revealed through genome-wide chromatin analysis of a higher eukaryote. , 2004, Genes & development.

[44]  D. Schlessinger,et al.  Transcriptome Analysis of Mouse Stem Cells and Early Embryos , 2003, PLoS biology.

[45]  Mark Gerstein,et al.  Millions of years of evolution preserved: a comprehensive catalog of the processed pseudogenes in the human genome. , 2003, Genome research.

[46]  Stuart L. Schreiber,et al.  Active genes are tri-methylated at K4 of histone H3 , 2002, Nature.

[47]  Stuart L. Schreiber,et al.  Methylation of histone H3 Lys 4 in coding regions of active genes , 2002, Proceedings of the National Academy of Sciences of the United States of America.

[48]  Frank Sleutels,et al.  The non-coding Air RNA is required for silencing autosomal imprinted genes , 2002, Nature.

[49]  E. Myers,et al.  Basic local alignment search tool. , 1990, Journal of molecular biology.

[50]  K. Kristiansen,et al.  Corrigendum: Ab initio reconstruction of cell type–specific transcriptomes in mouse reveals the conserved multi-exonic structure of lincRNAs , 2010, Nature Biotechnology.

[51]  D. Reidel,et al.  The Transcriptional Landscape of the Mammalian Genome The FANTOM Consortium* and RIKEN Genome Exploration Research Group and Genome Science Group (Genome Network Project Core Group)* , 2005 .

[52]  N. Nomura,et al.  Complete sequencing and characterization of 21,243 full-length human cDNAs , 2004, Nature Genetics.