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Nature Research, Nature, 7493(507), p. 455-461, 2014

DOI: 10.1038/nature12787

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An atlas of active enhancers across human cell types and tissues

Journal article published in 2014 by Michiel J. L. de Hoon, David A. de Lima Morais, Erik van Nimwegen, Marc van de Wetering, Linda M. van den Berg, Silvia Zucchelli, Takahiro Suzuki, Sebastian Schmeier, Christian Schmid, Ulf Schaefer, Charles Plessy, Morana Vitezic, Jessica Severin, Colin A. Semple, Robert S. Young and other authors.
This paper is made freely available by the publisher.
This paper is made freely available by the publisher.

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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 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.