An atlas of active enhancers across human cell types and tissues

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

doi:10.1038/nature12787

An atlas of active enhancers across human cell types and tissues

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

Hubrecht Institute

Onderzoeksoutput: Bijdrage aan wetenschappelijk tijdschrift/periodieke uitgave › Artikel › Wetenschappelijk › peer review

1861 Citaten (Scopus)

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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.

Originele taal-2	Engels
Pagina's (van-tot)	455-61
Aantal pagina's	7
Tijdschrift	Nature
Volume	507
Nummer van het tijdschrift	7493
DOI's	https://doi.org/10.1038/nature12787
Status	Gepubliceerd - 27 mrt. 2014

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10.1038/nature12787

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Andersson, R., Gebhard, C., Miguel-Escalada, I., Hoof, I., Bornholdt, J., Boyd, M., Chen, Y., Zhao, X., Schmidl, C., Suzuki, T., Ntini, E., Arner, E., Valen, E., Li, K., Schwarzfischer, L., Glatz, D., Raithel, J., Lilje, B., Rapin, N. (2014). An atlas of active enhancers across human cell types and tissues. Nature, 507(7493), 455-61. https://doi.org/10.1038/nature12787

@article{8709fc0092fa46dd9d5a2120704d117a,

title = "An atlas of active enhancers across human cell types and tissues",

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.",

keywords = "Atlases as Topic, Cell Line, Cells, Cultured, Cluster Analysis, Enhancer Elements, Genetic, Gene Expression Regulation, Genetic Predisposition to Disease, HeLa Cells, Humans, Molecular Sequence Annotation, Organ Specificity, Polymorphism, Single Nucleotide, Promoter Regions, Genetic, RNA, Messenger, Transcription Initiation Site, Transcription Initiation, Genetic",

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

year = "2014",

month = mar,

day = "27",

doi = "10.1038/nature12787",

language = "English",

volume = "507",

pages = "455--61",

journal = "Nature",

issn = "0028-0836",

publisher = "Nature Publishing Group",

number = "7493",

}

Andersson, R, Gebhard, C, Miguel-Escalada, I, Hoof, I, Bornholdt, J, Boyd, M, Chen, Y, Zhao, X, Schmidl, C, Suzuki, T, Ntini, E, Arner, E, Valen, E, Li, K, Schwarzfischer, L, Glatz, D, Raithel, J, Lilje, B, Rapin, N, Bagger, FO, Jørgensen, M, Andersen, PR, Bertin, N, Rackham, O, Burroughs, AM, Baillie, JK, Ishizu, Y, Shimizu, Y, Furuhata, E, Maeda, S, Negishi, Y, Mungall, CJ, Meehan, TF, Lassmann, T, Itoh, M, Kawaji, H, Kondo, N, Kawai, J, Lennartsson, A, Daub, CO, Heutink, P, Hume, DA, Jensen, TH, Suzuki, H, Hayashizaki, Y, Müller, F, Forrest, ARR, Carninci, P, Rehli, M 2014, 'An atlas of active enhancers across human cell types and tissues', Nature, vol. 507, nr. 7493, blz. 455-61. https://doi.org/10.1038/nature12787

TY - JOUR

T1 - An atlas of active enhancers across human cell types and tissues

AU - Andersson, Robin

AU - Gebhard, Claudia

AU - Miguel-Escalada, Irene

AU - Hoof, Ilka

AU - Bornholdt, Jette

AU - Boyd, Mette

AU - Chen, Yun

AU - Zhao, Xiaobei

AU - Schmidl, Christian

AU - Suzuki, Takahiro

AU - Ntini, Evgenia

AU - Arner, Erik

AU - Valen, Eivind

AU - Li, Kang

AU - Schwarzfischer, Lucia

AU - Glatz, Dagmar

AU - Raithel, Johanna

AU - Lilje, Berit

AU - Rapin, Nicolas

AU - Bagger, Frederik Otzen

AU - Jørgensen, Mette

AU - Andersen, Peter Refsing

AU - Bertin, Nicolas

AU - Rackham, Owen

AU - Burroughs, A Maxwell

AU - Baillie, J Kenneth

AU - Ishizu, Yuri

AU - Shimizu, Yuri

AU - Furuhata, Erina

AU - Maeda, Shiori

AU - Negishi, Yutaka

AU - Mungall, Christopher J

AU - Meehan, Terrence F

AU - Lassmann, Timo

AU - Itoh, Masayoshi

AU - Kawaji, Hideya

AU - Kondo, Naoto

AU - Kawai, Jun

AU - Lennartsson, Andreas

AU - Daub, Carsten O

AU - Heutink, Peter

AU - Hume, David A

AU - Jensen, Torben Heick

AU - Suzuki, Harukazu

AU - Hayashizaki, Yoshihide

AU - Müller, Ferenc

AU - Forrest, Alistair R R

AU - Carninci, Piero

AU - Rehli, Michael

AU - Clevers, Hans

PY - 2014/3/27

Y1 - 2014/3/27

N2 - 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.

AB - 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.

KW - Atlases as Topic

KW - Cell Line

KW - Cells, Cultured

KW - Cluster Analysis

KW - Enhancer Elements, Genetic

KW - Gene Expression Regulation

KW - Genetic Predisposition to Disease

KW - HeLa Cells

KW - Humans

KW - Molecular Sequence Annotation

KW - Organ Specificity

KW - Polymorphism, Single Nucleotide

KW - Promoter Regions, Genetic

KW - RNA, Messenger

KW - Transcription Initiation Site

KW - Transcription Initiation, Genetic

U2 - 10.1038/nature12787

DO - 10.1038/nature12787

M3 - Article

C2 - 24670763

SN - 0028-0836

VL - 507

SP - 455

EP - 461

JO - Nature

JF - Nature

IS - 7493

ER -

An atlas of active enhancers across human cell types and tissues

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