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An atlas of active enhancers across human cell types and tissues

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

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.

Atlases as Topic, Cell Line, Cells, Cultured, Cluster Analysis, Enhancer Elements, Genetic/genetics, Gene Expression Regulation/genetics, Genetic Predisposition to Disease/genetics, HeLa Cells, Humans, Molecular Sequence Annotation, Organ Specificity, Polymorphism, Single Nucleotide/genetics, Promoter Regions, Genetic/genetics, RNA, Messenger/biosynthesis, Transcription Initiation Site, Transcription Initiation, Genetic
0028-0836
455-461
Andersson, Robin
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Gebhard, Claudia
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Miguel-Escalada, Irene
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Hoof, Ilka
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Bornholdt, Jette
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Boyd, Mette
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Chen, Yun
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Zhao, Xiaobei
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Schmidl, Christian
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Suzuki, Takahiro
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Ntini, Evgenia
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Arner, Erik
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Valen, Eivind
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Li, Kang
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Schwarzfischer, Lucia
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Glatz, Dagmar
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Raithel, Johanna
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Lilje, Berit
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Rapin, Nicolas
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Jørgensen, Mette
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Andersen, Peter Refsing
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Bertin, Nicolas
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Rackham, Owen
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Burroughs, A. Maxwell
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Baillie, J. Kenneth
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Ishizu, Yuri
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Shimizu, Yuri
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Furuhata, Erina
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Maeda, Shiori
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Negishi, Yutaka
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Mungall, Christopher J.
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Meehan, Terrence F.
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Lassmann, Timo
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Itoh, Masayoshi
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Kawaji, Hideya
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Kondo, Naoto
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Kawai, Jun
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Lennartsson, Andreas
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Daub, Carsten O.
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Heutink, Peter
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Hume, David A.
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Jensen, Torben Heick
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Suzuki, Harukazu
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Hayashizaki, Yoshihide
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Müller, Ferenc
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Forrest, Alistair R.R.
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Carninci, Piero
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Rehli, Michael
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Sandelin, Albin
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Andersson, Robin
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Gebhard, Claudia
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Miguel-Escalada, Irene
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Hoof, Ilka
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Bornholdt, Jette
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Boyd, Mette
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Chen, Yun
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Zhao, Xiaobei
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Schmidl, Christian
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Suzuki, Takahiro
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Ntini, Evgenia
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Arner, Erik
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Valen, Eivind
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Li, Kang
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Schwarzfischer, Lucia
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Glatz, Dagmar
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Raithel, Johanna
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Lilje, Berit
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Rapin, Nicolas
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Bagger, Frederik Otzen
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Jørgensen, Mette
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Andersen, Peter Refsing
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Bertin, Nicolas
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Rackham, Owen
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Burroughs, A. Maxwell
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Baillie, J. Kenneth
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Ishizu, Yuri
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Shimizu, Yuri
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Furuhata, Erina
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Maeda, Shiori
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Negishi, Yutaka
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Mungall, Christopher J.
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Meehan, Terrence F.
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Lassmann, Timo
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Itoh, Masayoshi
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Kawaji, Hideya
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Kondo, Naoto
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Kawai, Jun
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Lennartsson, Andreas
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Daub, Carsten O.
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Heutink, Peter
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Hume, David A.
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Jensen, Torben Heick
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Suzuki, Harukazu
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Hayashizaki, Yoshihide
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Müller, Ferenc
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Forrest, Alistair R.R.
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Carninci, Piero
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Rehli, Michael
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Sandelin, Albin
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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, Jørgensen, 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, Müller, Ferenc, Forrest, Alistair R.R., Carninci, Piero, Rehli, Michael and Sandelin, Albin (2014) An atlas of active enhancers across human cell types and tissues. Nature, 507 (7493), 455-461. (doi:10.1038/nature12787).

Record type: Article

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 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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More information

Published date: 26 March 2014
Keywords: Atlases as Topic, Cell Line, Cells, Cultured, Cluster Analysis, Enhancer Elements, Genetic/genetics, Gene Expression Regulation/genetics, Genetic Predisposition to Disease/genetics, HeLa Cells, Humans, Molecular Sequence Annotation, Organ Specificity, Polymorphism, Single Nucleotide/genetics, Promoter Regions, Genetic/genetics, RNA, Messenger/biosynthesis, Transcription Initiation Site, Transcription Initiation, Genetic

Identifiers

Local EPrints ID: 446746
URI: http://eprints.soton.ac.uk/id/eprint/446746
ISSN: 0028-0836
PURE UUID: 5a31b3a9-f6b9-40f8-b056-16e7d75789f5
ORCID for Owen Rackham: ORCID iD orcid.org/0000-0002-4390-0872

Catalogue record

Date deposited: 19 Feb 2021 17:33
Last modified: 17 Mar 2024 04:03

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Contributors

Author: Robin Andersson
Author: Claudia Gebhard
Author: Irene Miguel-Escalada
Author: Ilka Hoof
Author: Jette Bornholdt
Author: Mette Boyd
Author: Yun Chen
Author: Xiaobei Zhao
Author: Christian Schmidl
Author: Takahiro Suzuki
Author: Evgenia Ntini
Author: Erik Arner
Author: Eivind Valen
Author: Kang Li
Author: Lucia Schwarzfischer
Author: Dagmar Glatz
Author: Johanna Raithel
Author: Berit Lilje
Author: Nicolas Rapin
Author: Frederik Otzen Bagger
Author: Mette Jørgensen
Author: Peter Refsing Andersen
Author: Nicolas Bertin
Author: Owen Rackham ORCID iD
Author: A. Maxwell Burroughs
Author: J. Kenneth Baillie
Author: Yuri Ishizu
Author: Yuri Shimizu
Author: Erina Furuhata
Author: Shiori Maeda
Author: Yutaka Negishi
Author: Christopher J. Mungall
Author: Terrence F. Meehan
Author: Timo Lassmann
Author: Masayoshi Itoh
Author: Hideya Kawaji
Author: Naoto Kondo
Author: Jun Kawai
Author: Andreas Lennartsson
Author: Carsten O. Daub
Author: Peter Heutink
Author: David A. Hume
Author: Torben Heick Jensen
Author: Harukazu Suzuki
Author: Yoshihide Hayashizaki
Author: Ferenc Müller
Author: Alistair R.R. Forrest
Author: Piero Carninci
Author: Michael Rehli
Author: Albin Sandelin

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