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  • An atlas of active enhancers across human cell types and tissues

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    Accepted Manuscript (AM)
    Author(s)
    Andersson, Robin
    Gebhard, Claudia
    Miguel-Escalada, Irene
    Hoof, Ilka
    Bornholdt, Jette
    Boyd, Mette
    Chen, Yun
    Zhao, Xiaobei
    Schmidl, Christian
    Suzuki, Takahiro
    Ntini, Evgenia
    Arner, Erik
    Valen, Eivind
    Li, Kang
    Schwarzfischer, Lucia
    Glatz, Dagmar
    Raithel, Johanna
    Lilje, Berit
    Rapin, Nicolas
    Bagger, Frederik Otzen
    Jorgensen, Mette
    Andersen, Peter Refsing
    Bertin, Nicolas
    Rackham, Owen
    Burroughs, A Maxwell
    Baillie, J Kenneth
    Ishizu, Yuri
    Shimizu, Yuri
    Furuhata, Erina
    Maeda, Shiori
    Negishi, Yutaka
    Mungall, Christopher J
    Meehan, Terrence F
    Lassmann, Timo
    Itoh, Masayoshi
    Kawaji, Hideya
    Kondo, Naoto
    Kawai, Jun
    Lennartsson, Andreas
    Daub, Carsten O
    Heutink, Peter
    Hume, David A
    Jensen, Torben Heick
    Suzuki, Harukazu
    Hayashizaki, Yoshihide
    Mueller, Ferenc
    Forrest, Alistair RR
    Carninci, Piero
    Rehli, Michael
    Sandelin, Albin
    Griffith University Author(s)
    Mackay-Sim, Alan
    Year published
    2014
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    Abstract
    Enhancers control the correct temporal and cell-type-specific activation of gene expression in multicellular eukaryotes. Knowing their properties, regulatory activity and targets is crucial to understand the regulation of differentiation and homeostasis. Here we use the FANTOM5 panel of samples, covering the majority of human tissues and cell types, to produce an atlas of active, in vivo-transcribed enhancers. We show that enhancers share properties with CpG-poor messenger RNA promoters but produce bidirectional, exosome-sensitive, relatively short unspliced RNAs, the generation of which is strongly related to enhancer ...
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    Enhancers control the correct temporal and cell-type-specific activation of gene expression in multicellular eukaryotes. Knowing their properties, regulatory activity and targets is crucial to understand the regulation of differentiation and homeostasis. Here we use the FANTOM5 panel of samples, covering the majority of human tissues and cell types, to produce an atlas of active, in vivo-transcribed enhancers. We show that enhancers share properties with CpG-poor messenger RNA promoters but produce bidirectional, exosome-sensitive, relatively short unspliced RNAs, the generation of which is strongly related to enhancer activity. The atlas is used to compare regulatory programs between different cells at unprecedented depth, to identify disease-associated regulatory single nucleotide polymorphisms, and to classify cell-type-specific and ubiquitous enhancers. We further explore the utility of enhancer redundancy, which explains gene expression strength rather than expression patterns. The online FANTOM5 enhancer atlas represents a unique resource for studies on cell-type-specific enhancers and gene regulation.
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    Journal Title
    Nature
    Volume
    507
    DOI
    https://doi.org/10.1038/nature12787
    Copyright Statement
    © 2014 Nature Publishing Group. This is the author-manuscript version of this paper. Reproduced in accordance with the copyright policy of the publisher. Please refer to the journal website for access to the definitive, published version.
    Subject
    Science, technology and engineering curriculum and pedagogy
    Publication URI
    http://hdl.handle.net/10072/102456
    Collection
    • Journal articles

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