An atlas of active enhancers across human cell types and tissues

被引：1768

作者：

Andersson, Robin ^{[1
,2
]}

Gebhard, Claudia ^{[3
,4
]}

Miguel-Escalada, Irene ^{[5
]}

Hoof, Ilka ^{[1
,2
]}

Bornholdt, Jette ^{[1
,2
]}

Boyd, Mette ^{[1
,2
]}

Chen, Yun ^{[1
,2
]}

Zhao, Xiaobei ^{[1
,2
,6
]}

Schmidl, Christian ^{[3
]}

Suzuki, Takahiro ^{[7
,8
]}

Ntini, Evgenia ^{[9
]}

Arner, Erik ^{[7
,8
]}

Valen, Eivind ^{[1
,2
,10
]}

Li, Kang ^{[1
,2
]}

Schwarzfischer, Lucia ^{[3
]}

Glatz, Dagmar ^{[3
]}

Raithel, Johanna ^{[3
]}

Lilje, Berit ^{[1
,2
]}

Rapin, Nicolas ^{[1
,2
,11
,12
]}

Bagger, Frederik Otzen ^{[1
,2
,11
,12
]}

Jorgensen, Mette ^{[1
,2
]}

Andersen, Peter Refsing ^{[9
]}

Bertin, Nicolas ^{[7
,8
]}

Rackham, Owen ^{[7
,8
]}

Burroughs, A. Maxwell ^{[7
,8
]}

Baillie, J. Kenneth ^{[13
]}

Ishizu, Yuri ^{[7
,8
]}

Shimizu, Yuri ^{[7
,8
]}

Furuhata, Erina ^{[7
,8
]}

Maeda, Shiori ^{[7
,8
]}

Negishi, Yutaka ^{[7
,8
]}

Mungall, Christopher J. ^{[14
]}

Meehan, Terrence F. ^{[15
]}

Lassmann, Timo ^{[7
,8
]}

Itoh, Masayoshi ^{[7
,8
,16
]}

Kawaji, Hideya ^{[7
,16
]}

Kondo, Naoto ^{[7
,16
]}

Kawai, Jun ^{[7
,16
]}

Lennartsson, Andreas ^{[17
]}

Daub, Carsten O. ^{[7
,8
,17
]}

Heutink, Peter

Hume, David A. ^{[7
,13
]}

Jensen, Torben Heick ^{[9
]}

Suzuki, Harukazu ^{[7
,8
]}

Hayashizaki, Yoshihide ^{[7
,18
]}

Mueller, Ferenc ^{[5
]}

Forrest, Alistair R. R. ^{[7
,8
]}

Carninci, Piero ^{[7
,8
]}

Rehli, Michael ^{[3
,4
]}

Sandelin, Albin ^{[1
,2
]}

机构：

[1] Univ Copenhagen, Dept Biol, Bioinformat Ctr, DK-2200 Copenhagen, Denmark

[2] Univ Copenhagen, Biotech Res & Innovat Ctr, DK-2200 Copenhagen, Denmark

[3] Univ Hosp Regensburg, Dept Internal Med 3, D-93042 Regensburg, Germany

[4] Regensburg Ctr Intervent Immunol RCI, D-93042 Regensburg, Germany

[5] Univ Birmingham, Sch Clin & Expt Med, Coll Med & Dent Sci, Birmingham B15 2TT, W Midlands, England

[6] Univ N Carolina, Lineberger Comprehens Canc Ctr, Chapel Hill, NC 27599 USA

[7] RIKEN Yokohama Inst, RIKEN OMICS Sci Ctr, Yokohama, Kanagawa 2300045, Japan

[8] RIKEN Yokohama Inst, RIKEN Ctr Life Sci Technol, Div Genom Technol, Tsurumi Ku, Yokohama, Kanagawa 2300045, Japan

[9] Ctr mRNP Biogenesis & Metab, Dept Mol Biol & Genet, DK-8000 Aarhus, Denmark

[10] Harvard Univ, Dept Mol & Cellular Biol, Cambridge, MA 02138 USA

[11] Univ Copenhagen, Finsen Lab, Rigshosp, DK-2200 Copenhagen, Denmark

[12] Univ Copenhagen, Danish Stem Cell Ctr DanStem, DK-2200 Copenhagen, Denmark

[13] Univ Edinburgh, Roslin Inst, Edinburgh EH25 9RG, Midlothian, Scotland

[14] Univ Calif Berkeley, Lawrence Berkeley Natl Lab, Genom Div, Berkeley, CA 94720 USA

[15] EMBL Outstn Hinxton, European Bioinformat Inst, Cambridge CB10 1SD, England

[16] RIKEN Yokohama Inst, RIKEN Prevent Med & Diag Innovat Program, Tsurumi Ku, Yokohama, Kanagawa 2300045, Japan

[17] Karolinska Inst, Dept Biosci & Nutr, SE-4183 Stockholm, Sweden

[18] Vrije Univ Amsterdam, Med Ctr, Dept Clin Genet, NL-1081 BT Amsterdam, Netherlands

来源：

NATURE | 2014年 / 507卷 / 7493期

基金：

欧洲研究理事会; 英国生物技术与生命科学研究理事会;

关键词：

TRANSCRIPTION FACTORS; GENE-EXPRESSION; CAP-ANALYSIS; REGULATORY SEQUENCES; DNA METHYLATION; DISCOVERY; INFORMATION; LANDSCAPE; UPSTREAM; PATTERN;

D O I：

10.1038/nature12787

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

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.

引用

页码：455 / +

页数：13

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