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  • 1
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    Landscape of transcription in human cells (2012)
    Nature Publishing Group (NPG)
    Details
    Publication Date: 2012-09-08
    Description: Eukaryotic cells make many types of primary and processed RNAs that are found either in specific subcellular compartments or throughout the cells. A complete catalogue of these RNAs is not yet available and their characteristic subcellular localizations are also poorly understood. Because 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, modification 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 a redefinition of the concept of a gene.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3684276/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3684276/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Djebali, Sarah -- Davis, Carrie A -- Merkel, Angelika -- Dobin, Alex -- Lassmann, Timo -- Mortazavi, Ali -- Tanzer, Andrea -- Lagarde, Julien -- Lin, Wei -- Schlesinger, Felix -- Xue, Chenghai -- Marinov, Georgi K -- Khatun, Jainab -- Williams, Brian A -- Zaleski, Chris -- Rozowsky, Joel -- Roder, Maik -- Kokocinski, Felix -- Abdelhamid, Rehab F -- Alioto, Tyler -- Antoshechkin, Igor -- Baer, Michael T -- Bar, Nadav S -- Batut, Philippe -- Bell, Kimberly -- Bell, Ian -- Chakrabortty, Sudipto -- Chen, Xian -- Chrast, Jacqueline -- Curado, Joao -- Derrien, Thomas -- Drenkow, Jorg -- Dumais, Erica -- Dumais, Jacqueline -- Duttagupta, Radha -- Falconnet, Emilie -- Fastuca, Meagan -- Fejes-Toth, Kata -- Ferreira, Pedro -- Foissac, Sylvain -- Fullwood, Melissa J -- Gao, Hui -- Gonzalez, David -- Gordon, Assaf -- Gunawardena, Harsha -- Howald, Cedric -- Jha, Sonali -- Johnson, Rory -- Kapranov, Philipp -- King, Brandon -- Kingswood, Colin -- Luo, Oscar J -- Park, Eddie -- Persaud, Kimberly -- Preall, Jonathan B -- Ribeca, Paolo -- Risk, Brian -- Robyr, Daniel -- Sammeth, Michael -- Schaffer, Lorian -- See, Lei-Hoon -- Shahab, Atif -- Skancke, Jorgen -- Suzuki, Ana Maria -- Takahashi, Hazuki -- Tilgner, Hagen -- Trout, Diane -- Walters, Nathalie -- Wang, Huaien -- Wrobel, John -- Yu, Yanbao -- Ruan, Xiaoan -- Hayashizaki, Yoshihide -- Harrow, Jennifer -- Gerstein, Mark -- Hubbard, Tim -- Reymond, Alexandre -- Antonarakis, Stylianos E -- Hannon, Gregory -- Giddings, Morgan C -- Ruan, Yijun -- Wold, Barbara -- Carninci, Piero -- Guigo, Roderic -- Gingeras, Thomas R -- 062023/Wellcome Trust/United Kingdom -- 1RC2HG005591/HG/NHGRI NIH HHS/ -- 249968/European Research Council/International -- P30 CA045508/CA/NCI NIH HHS/ -- R01 HG003700/HG/NHGRI NIH HHS/ -- R01HG003700/HG/NHGRI NIH HHS/ -- R37 GM062534/GM/NIGMS NIH HHS/ -- RC2 HG005591/HG/NHGRI NIH HHS/ -- U01 HG003147/HG/NHGRI NIH HHS/ -- U54 HG004555/HG/NHGRI NIH HHS/ -- U54 HG004557/HG/NHGRI NIH HHS/ -- U54 HG004558/HG/NHGRI NIH HHS/ -- U54 HG004576/HG/NHGRI NIH HHS/ -- U54 HG007004/HG/NHGRI NIH HHS/ -- U54HG004555/HG/NHGRI NIH HHS/ -- U54HG004557/HG/NHGRI NIH HHS/ -- U54HG004558/HG/NHGRI NIH HHS/ -- U54HG004576/HG/NHGRI NIH HHS/ -- England -- Nature. 2012 Sep 6;489(7414):101-8. doi: 10.1038/nature11233.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Centre for Genomic Regulation and UPF, Doctor Aiguader 88, Barcelona 08003, Catalonia, Spain.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/22955620" target="_blank"〉PubMed〈/a〉
    Keywords: Alleles ; Cell Line ; DNA/*genetics ; DNA, Intergenic/genetics ; *Encyclopedias as Topic ; Enhancer Elements, Genetic ; Exons/genetics ; Gene Expression Profiling ; Genes/genetics ; Genome, Human/*genetics ; Genomics ; Humans ; *Molecular Sequence Annotation ; Polyadenylation/genetics ; Protein Isoforms/genetics ; RNA/biosynthesis/genetics ; RNA Editing/genetics ; RNA Splicing/genetics ; Regulatory Sequences, Nucleic Acid/*genetics ; Repetitive Sequences, Nucleic Acid/genetics ; Sequence Analysis, RNA ; Transcription, Genetic/*genetics ; Transcriptome/*genetics
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
    Published by Nature Publishing Group (NPG)
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  • 2
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    Domains of genome-wide gene expression dysregulation in Down's syndrome (2014)
    Nature Publishing Group (NPG)
    Details
    Publication Date: 2014-04-18
    Description: Trisomy 21 is the most frequent genetic cause of cognitive impairment. To assess the perturbations of gene expression in trisomy 21, and to eliminate the noise of genomic variability, we studied the transcriptome of fetal fibroblasts from a pair of monozygotic twins discordant for trisomy 21. Here we show that the differential expression between the twins is organized in domains along all chromosomes that are either upregulated or downregulated. These gene expression dysregulation domains (GEDDs) can be defined by the expression level of their gene content, and are well conserved in induced pluripotent stem cells derived from the twins' fibroblasts. Comparison of the transcriptome of the Ts65Dn mouse model of Down's syndrome and normal littermate mouse fibroblasts also showed GEDDs along the mouse chromosomes that were syntenic in human. The GEDDs correlate with the lamina-associated (LADs) and replication domains of mammalian cells. The overall position of LADs was not altered in trisomic cells; however, the H3K4me3 profile of the trisomic fibroblasts was modified and accurately followed the GEDD pattern. These results indicate that the nuclear compartments of trisomic cells undergo modifications of the chromatin environment influencing the overall transcriptome, and that GEDDs may therefore contribute to some trisomy 21 phenotypes.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Letourneau, Audrey -- Santoni, Federico A -- Bonilla, Ximena -- Sailani, M Reza -- Gonzalez, David -- Kind, Jop -- Chevalier, Claire -- Thurman, Robert -- Sandstrom, Richard S -- Hibaoui, Youssef -- Garieri, Marco -- Popadin, Konstantin -- Falconnet, Emilie -- Gagnebin, Maryline -- Gehrig, Corinne -- Vannier, Anne -- Guipponi, Michel -- Farinelli, Laurent -- Robyr, Daniel -- Migliavacca, Eugenia -- Borel, Christelle -- Deutsch, Samuel -- Feki, Anis -- Stamatoyannopoulos, John A -- Herault, Yann -- van Steensel, Bas -- Guigo, Roderic -- Antonarakis, Stylianos E -- U54HG007010/HG/NHGRI NIH HHS/ -- England -- Nature. 2014 Apr 17;508(7496):345-50. doi: 10.1038/nature13200.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉1] Department of Genetic Medicine and Development, University of Geneva Medical School, University Hospitals of Geneva, 1211 Geneva, Switzerland [2]. ; Department of Genetic Medicine and Development, University of Geneva Medical School, University Hospitals of Geneva, 1211 Geneva, Switzerland. ; Center for Genomic Regulation, University Pompeu Fabra, 08003 Barcelona, Spain. ; Division of Gene Regulation, Netherlands Cancer Institute, 1066 CX Amsterdam, The Netherlands. ; AneuPath 21, Institut de Genetique Biologie Moleculaire et Cellulaire, Translational medicine and Neuroscience program, IGBMC, ICS, PHENOMIN, CNRS, INSERM, Universite de Strasbourg, UMR7104, UMR964, 1 rue Laurent Fries, 67404 Illkirch, France. ; Department of Genome Sciences, University of Washington, Seattle, Washington 98195, USA. ; Stem Cell Research Laboratory, Department of Obstetrics and Gynecology, Geneva University Hospitals, 1211 Geneva, Switzerland. ; FASTERIS SA, 1228 Plan-les-Ouates, Switzerland. ; 1] Department of Genetic Medicine and Development, University of Geneva Medical School, University Hospitals of Geneva, 1211 Geneva, Switzerland [2] Swiss Institute of Bioinfomatics, 1211 Geneva, Switzerland. ; DOE Joint Genome Institute, Walnut Creek, California 94598, USA. ; 1] Department of Genetic Medicine and Development, University of Geneva Medical School, University Hospitals of Geneva, 1211 Geneva, Switzerland [2] iGE3 Institute of Genetics and Genomics of Geneva, 1211 Geneva, Switzerland.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24740065" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Cells, Cultured ; Chromatin/chemistry/metabolism ; Chromosomes, Human, Pair 21/genetics ; Chromosomes, Mammalian/genetics ; DNA Replication Timing ; Down Syndrome/*genetics/pathology ; Female ; Fetus/cytology ; Fibroblasts ; Gene Expression Regulation/*genetics ; Genome/*genetics ; Histones/chemistry/metabolism ; Humans ; Induced Pluripotent Stem Cells/metabolism ; Lysine/metabolism ; Male ; Methylation ; Mice ; Transcriptome/*genetics ; Twins, Monozygotic/genetics
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
    Published by Nature Publishing Group (NPG)
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  • 3
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    Corrigendum: Domains of genome-wide gene expression dysregulation in Down's syndrome (2015)
    Nature Publishing Group (NPG)
    Details
    Publication Date: 2015-12-04
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Letourneau, Audrey -- Santoni, Federico A -- Bonilla, Ximena -- Sailani, M Reza -- Gonzalez, David -- Kind, Jop -- Chevalier, Claire -- Thurman, Robert -- Sandstrom, Richard S -- Hibaoui, Youssef -- Garieri, Marco -- Popadin, Konstantin -- Falconnet, Emilie -- Gagnebin, Maryline -- Gehrig, Corinne -- Vannier, Anne -- Guipponi, Michel -- Farinelli, Laurent -- Robyr, Daniel -- Migliavacca, Eugenia -- Borel, Christelle -- Deutsch, Samuel -- Feki, Anis -- Stamatoyannopoulos, John A -- Herault, Yann -- van Steensel, Bas -- Guigo, Roderic -- Antonarakis, Stylianos E -- England -- Nature. 2016 Mar 17;531(7594):400. doi: 10.1038/nature16135. Epub 2015 Dec 2.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/26633627" target="_blank"〉PubMed〈/a〉
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
    Published by Nature Publishing Group (NPG)
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  • 4
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    Chromatin three-dimensional interactions mediate genetic effects on gene expression (2019)
    American Association for the Advancement of Science (AAAS)
    In: Science
    Details
    Publication Date: 2019
    Description: 〈p〉Studying the genetic basis of gene expression and chromatin organization is key to characterizing the effect of genetic variability on the function and structure of the human genome. Here we unravel how genetic variation perturbs gene regulation using a dataset combining activity of regulatory elements, gene expression, and genetic variants across 317 individuals and two cell types. We show that variability in regulatory activity is structured at the intra- and interchromosomal levels within 12,583 cis-regulatory domains and 30 trans-regulatory hubs that highly reflect the local (that is, topologically associating domains) and global (that is, open and closed chromatin compartments) nuclear chromatin organization. These structures delimit cell type–specific regulatory networks that control gene expression and coexpression and mediate the genetic effects of cis- and trans-acting regulatory variants on genes.〈/p〉
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
    Published by American Association for the Advancement of Science (AAAS)
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  • 5
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    Chromatin three-dimensional interactions mediate genetic effects on gene expression (2019)
    American Association for the Advancement of Science
    Details
    Publication Date: 2019-05-03
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
    Published by American Association for the Advancement of Science
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