An atlas of active enhancers across human cell types and tissues

  title={An atlas of active enhancers across human cell types and tissues},
  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 Frederik Otzen Bagger and Mette J{\o}rgensen and Peter Refsing Andersen and Nicolas Bertin and Owen J. L. Rackham and A. Maxwell Burroughs and John Kenneth Baillie and Yuri Ishizu and Yuri Shimizu and Erina Furuhata and Shiori Maeda and Yutaka Negishi and Chris J. Mungall and Terrence F. Meehan and Timo Lassmann and Masayoshi Itoh and Hideya Kawaji and Naoto Kondo and Jun Kawai and Andreas Lennartsson and Carsten O. Daub and Peter Heutink and David A. Hume and Torben Heick Jensen and Harukazu Suzuki and Yoshihide Hayashizaki and Ferenc M{\"u}ller and Alistair R. R. Forrest and Piero Carninci and Michael Rehli and Albin Sandelin},
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… 

Motif signatures of transcribed enhancers

This work used TELS to compile a comprehensive catalog of motif signatures for all known TrEn identified by the FANTOM5 consortium across 112 human primary cells and tissues, and confirms that distinct cell type/tissue specific motif signatures characterize TrEn.

Super-enhancers are transcriptionally more active and cell-type-specific than stretch enhancers

A comparative analysis of super and stretch enhancers with respect to their chromatin profiles, cell-type-specificity, and ability to control gene expression suggests that super-enhancers are transcriptionally more active and cell- type-specific than stretch enhancer.

Identification of cell states using super-enhancer RNA

The proposed super-enhancer RNAs can act as a good alternative, without the complicated measurement of histone modifications, for identifying important regulatory elements of cell type specification and identifying dynamic cell states.

Enhancer dependence of cell-type–specific gene expression increases with developmental age

It is concluded that the progressively increased enhancer dependence of cell-type–specific genes with developmental age is conserved during development, characterized by simpler promoter-centric regulation of cell–type-specific genes in embryonic cells and increased combinatorial enhancer-driven control in adult cells.

The selection and function of cell type-specific enhancers

The human body contains several hundred cell types, all of which share the same genome, and much of the regulatory code that drives cell type-specific gene expression is located in distal elements called enhancers, which influences the functions of enhancers and super-enhancers.

A promoter-level mammalian expression atlas

It is found that few genes are truly ‘housekeeping’, whereas many mammalian promoters are composite entities composed of several closely separated TSSs, with independent cell-type-specific expression profiles.

Transcriptionally active enhancers in human cancer cells

The growth of human cancer cells is driven by aberrant enhancer and gene transcription activity. Here, we use transient transcriptome sequencing (TT‐seq) to map thousands of transcriptionally active

Transcribed enhancers lead waves of coordinated transcription in transitioning mammalian cells

The data support a highly generalizable model in which enhancer transcription is the earliest event in successive waves of transcriptional change during cellular differentiation or activation.

Histone modifications at human enhancers reflect global cell-type-specific gene expression

The results define over 55,000 potential transcriptional enhancers in the human genome, significantly expanding the current catalogue of human enhancers and highlighting the role of these elements in cell-type-specific gene expression.

A promoter-level mammalian expression atlas

It is found that few genes are truly ‘housekeeping’, whereas many mammalian promoters are composite entities composed of several closely separated TSSs, with independent cell-type-specific expression profiles.

A unique chromatin signature uncovers early developmental enhancers in humans

It is demonstrated that early developmental enhancers are epigenetically pre-marked in hESCs and indicate an unappreciated role of H3K27me3 at distal regulatory elements.

The accessible chromatin landscape of the human genome

The first extensive map of human DHSs identified through genome-wide profiling in 125 diverse cell and tissue types is presented, revealing novel relationships between chromatin accessibility, transcription, DNA methylation and regulatory factor occupancy patterns.

Systematic dissection of regulatory motifs in 2000 predicted human enhancers using a massively parallel reporter assay.

A massively parallel reporter assay is used to measure transcriptional levels induced by 145-bp DNA segments centered on evolutionarily conserved regulatory motif instances within enhancer chromatin states and finds statistically robust evidence that disrupting the predicted activator motifs abolishes enhancer function.

Genome-wide analysis of mammalian promoter architecture and evolution

These tagging methods allow quantitative analysis of promoter usage in different tissues and show that differentially regulated alternative TSSs are a common feature in protein-coding genes and commonly generate alternative N termini.

Widespread transcription at neuronal activity-regulated enhancers

It is revealed that a widespread mechanism of enhancer activation involves RNAPII binding and eRNA synthesis, which occurs specifically at enhancers that are actively engaged in promoting mRNA synthesis.

Characterization of genome-wide enhancer-promoter interactions reveals co-expression of interacting genes and modes of higher order chromatin organization

The results define a global view of EP interactions and provide a data set to further understand mechanisms of enhancer targeting and long-range chromatin organization and find that chromosomes are organized into multiple levels of interacting domains.