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      Landscape of transcription in human cells

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          Summary

          Eukaryotic cells make many types of primary and processed RNAs that are found either in specific sub-cellular compartments or throughout the cells. A complete catalogue of these RNAs is not yet available and their characteristic sub-cellular localizations are also poorly understood. Since RNA represents the direct output of the genetic information encoded by genomes and a significant proportion of a cell’s regulatory capabilities are focused on its synthesis, processing, transport, modifications and translation, the generation of such a catalogue is crucial for understanding genome function. Here we report evidence that three quarters of the human genome is capable of being transcribed, as well as observations about the range and levels of expression, localization, processing fates, regulatory regions and modifications of almost all currently annotated and thousands of previously unannotated RNAs. These observations taken together prompt to a redefinition of the concept of a gene.

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          Most cited references32

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          RNA maps reveal new RNA classes and a possible function for pervasive transcription.

          Significant fractions of eukaryotic genomes give rise to RNA, much of which is unannotated and has reduced protein-coding potential. The genomic origins and the associations of human nuclear and cytosolic polyadenylated RNAs longer than 200 nucleotides (nt) and whole-cell RNAs less than 200 nt were investigated in this genome-wide study. Subcellular addresses for nucleotides present in detected RNAs were assigned, and their potential processing into short RNAs was investigated. Taken together, these observations suggest a novel role for some unannotated RNAs as primary transcripts for the production of short RNAs. Three potentially functional classes of RNAs have been identified, two of which are syntenically conserved and correlate with the expression state of protein-coding genes. These data support a highly interleaved organization of the human transcriptome.
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            The ENCODE (ENCyclopedia Of DNA Elements) Project.

            The ENCyclopedia Of DNA Elements (ENCODE) Project aims to identify all functional elements in the human genome sequence. The pilot phase of the Project is focused on a specified 30 megabases (approximately 1%) of the human genome sequence and is organized as an international consortium of computational and laboratory-based scientists working to develop and apply high-throughput approaches for detecting all sequence elements that confer biological function. The results of this pilot phase will guide future efforts to analyze the entire human genome.
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              Is Open Access

              Integrative annotation of chromatin elements from ENCODE data

              The ENCODE Project has generated a wealth of experimental information mapping diverse chromatin properties in several human cell lines. Although each such data track is independently informative toward the annotation of regulatory elements, their interrelations contain much richer information for the systematic annotation of regulatory elements. To uncover these interrelations and to generate an interpretable summary of the massive datasets of the ENCODE Project, we apply unsupervised learning methodologies, converting dozens of chromatin datasets into discrete annotation maps of regulatory regions and other chromatin elements across the human genome. These methods rediscover and summarize diverse aspects of chromatin architecture, elucidate the interplay between chromatin activity and RNA transcription, and reveal that a large proportion of the genome lies in a quiescent state, even across multiple cell types. The resulting annotation of non-coding regulatory elements correlate strongly with mammalian evolutionary constraint, and provide an unbiased approach for evaluating metrics of evolutionary constraint in human. Lastly, we use the regulatory annotations to revisit previously uncharacterized disease-associated loci, resulting in focused, testable hypotheses through the lens of the chromatin landscape.
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                Author and article information

                Journal
                0410462
                6011
                Nature
                Nature
                Nature
                0028-0836
                1476-4687
                6 June 2013
                6 September 2012
                17 June 2013
                : 489
                : 7414
                : 101-108
                Affiliations
                [1 ]Centre for Genomic Regulation (CRG) and UPF, Doctor Aiguader, 88 . Barcelona, Catalunya, Spain 08003.
                [2 ]Cold Spring Harbor Laboratory, Functional Genomics, 1 Bungtown Rd. Cold Spring Harbor, NY, USA 11742.
                [3 ]Affymetrix, Inc, 3380 Central Expressway, Santa Clara, CA. USA 95051.
                [4 ]Boise State University, College of Arts & Sciences, 1910 University Dr. Boise, ID USA 83725.
                [5 ]California Institute of Technology, Division of Biology, 91125. 2 Beckman Institute, Pasadena, CA USA 91125.
                [6 ]Genome Institute of Singapore, Genome Technology and Biology, 60 Biopolis Street, #02-01, Genome, Singapore, Singapore 138672.
                [7 ]RIKEN Yokohama Institute, RIKEN Omics Science Center, 1-7-22 Suehiro-cho, Tsurumi-ku, Yokohama, Kanagawa Japan 230-0045.
                [8 ]University of California Irvine, Dept of. Developmental and Cell Biology, 2300 Biological Sciences III, Irving, CA USA 92697.
                [9 ]University of Geneva Medical School, Department of Genetic Medicine and Development and iGE3 Institute of Genetics and Genomics of Geneva, 1 rue Michel-Servet, Geneva, Switzerland 1015.
                [10 ]University of Lausanne, Center for Integrative Genomics, Genopode building, Lausanne, Switzerland 1015.
                [11 ]University of North Carolina at Chapel Hill, Department of Biochemistry & Biophysics, 120 Mason Farm Rd., Chapel Hill, NC USA 27599.
                [12 ]Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridgeshire United Kingdom CB10 1SA.
                [13 ]Program in Computational Biology and Bioinformatics, Yale University, Bass 432, 266 Whitney Avenue, New Haven, CT 06520.
                [14 ]Department of Molecular Biophysics and Biochemistry, Yale University, Bass 432, 266 Whitney Avenue, New Haven, CT 06520.
                [15 ]Department of Computer Science, Yale University, Bass 432, 266 Whitney Avenue, New Haven, CT 06520.
                [16 ]St. Laurent Institute, One Kendall Square, Cambridge, MA.
                [17 ]Department of Chemical Engineering, Norwegian University of Science and Technology (NTNU), Trondheim, Norway.
                Author notes
                Corresponding Authors: - Thomas R. Gingeras, Cold Spring Harbor Laboratory. gingeras@ 123456cshl.edu - Roderic Guigó, Centre for Genomic Regulation. roderic.guigo@ 123456crg.eu
                [*]

                These authors contributed equally to this work

                Article
                NIHMS377835
                10.1038/nature11233
                3684276
                22955620
                587ef1b4-0dde-4aed-95fc-3f3ec61405a2

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                History
                Funding
                Funded by: National Human Genome Research Institute : NHGRI
                Award ID: U54 HG007004 || HG
                Funded by: National Human Genome Research Institute : NHGRI
                Award ID: U54 HG004557 || HG
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