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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.

SUBMITTER: Andersson R 

PROVIDER: S-EPMC5215096 | biostudies-literature | 2014 Mar

REPOSITORIES: biostudies-literature

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

Andersson Robin R   Gebhard Claudia C   Miguel-Escalada Irene I   Hoof Ilka I   Bornholdt Jette J   Boyd Mette M   Chen Yun Y   Zhao Xiaobei X   Schmidl Christian C   Suzuki Takahiro T   Ntini Evgenia E   Arner Erik E   Valen Eivind E   Li Kang K   Schwarzfischer Lucia L   Glatz Dagmar D   Raithel Johanna J   Lilje Berit B   Rapin Nicolas N   Bagger Frederik Otzen FO   Jørgensen Mette M   Andersen Peter Refsing PR   Bertin Nicolas N   Rackham Owen O   Burroughs A Maxwell AM   Baillie J Kenneth JK   Ishizu Yuri Y   Shimizu Yuri Y   Furuhata Erina E   Maeda Shiori S   Negishi Yutaka Y   Mungall Christopher J CJ   Meehan Terrence F TF   Lassmann Timo T   Itoh Masayoshi M   Kawaji Hideya H   Kondo Naoto N   Kawai Jun J   Lennartsson Andreas A   Daub Carsten O CO   Heutink Peter P   Hume David A DA   Jensen Torben Heick TH   Suzuki Harukazu H   Hayashizaki Yoshihide Y   Müller Ferenc F   Forrest Alistair R R ARR   Carninci Piero P   Rehli Michael M   Sandelin Albin A  

Nature 20140301 7493


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 prod  ...[more]

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