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

View ORCID ProfileAziz Khan, View ORCID ProfileAnthony Mathelier, View ORCID ProfileXuegong Zhang
doi: https://doi.org/10.1101/310839
Aziz Khan
1Centre for Molecular Medicine Norway (NCMM), Nordic EMBL Partnership, University of Oslo, Oslo, Norway
2Key Lab of Bioinformatics/Bioinformatics Division, BNRIST (Beijing National Research Center for Information Science and Technology), Department of Automation, Tsinghua University, Beijing 100084, China
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  • For correspondence: aziz.khan@ncmm.uio.no
Anthony Mathelier
1Centre for Molecular Medicine Norway (NCMM), Nordic EMBL Partnership, University of Oslo, Oslo, Norway
3Department of Cancer Genetics, Institute for Cancer Research, Oslo University Hospital Radiumhospitalet, 0372 Oslo, Norway
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Xuegong Zhang
2Key Lab of Bioinformatics/Bioinformatics Division, BNRIST (Beijing National Research Center for Information Science and Technology), Department of Automation, Tsinghua University, Beijing 100084, China
4School of Life Sciences, Tsinghua University, Beijing, 100084, China
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Abstract

Background Super-enhancers and stretch enhancers represent classes of transcriptional enhancers that have been shown to control the expression of cell identity genes and carry disease- and trait-associated variants. Specifically, super-enhancers are clusters of enhancers defined based on the binding occupancy of master transcription factors (TFs), chromatin regulators, or chromatin marks, while stretch enhancers are large chromatin-defined regulatory regions of at least 3,000 base pairs. Several studies have characterized these regulatory regions in numerous cell types and tissues to decipher their functional importance. However, the differences and similarities between these regulatory regions have not been fully assessed.

Results We integrated genomic, epigenomic, and transcriptomic data from ten human cell types to perform a comparative analysis of super and stretch enhancers with respect to their chromatin profiles, cell-type-specificity, and ability to control gene expression. We found that stretch enhancers are more abundant, more distal to transcription start sites, cover twice as much the genome and are significantly less conserved than super-enhancers. In contrast, super-enhancers are significantly more enriched for active chromatin marks and cohesin complex and transcriptionally active than stretch enhancers. Importantly, a vast majority of superenhancers (85%) overlap with only a small subset of stretch enhancers (13%), which are enriched for cell-type-specific biological functions, and control cell identity genes.

Conclusions These results suggest that super-enhancers are transcriptionally more active and cell-type-specific than stretch enhancers, and importantly, most of the stretch enhancers that are distinct from superenhancers do not show an association with cell identity genes, are less active, and more likely to be poised enhancers.

  • List of abbreviations

    TFs
    : Transcription Factors;
    ChIP-seq
    : Chromatin immune precipitation followed by high-throughput sequencing;
    ES
    : Embryonic Stem;
    SEs
    : Super-enhancers;
    LCR
    : Locus Control Regions;
    TSS
    : Transcription Start Site;
    GO
    : Gene Ontology;
    GRO-seq
    : Global run-on sequencing;
    GRO-cap
    : Global run-on sequencing coupled with enrichment for nascent RNAs with 5’caps;
    ENCODE
    : Encyclopedia of Regulatory DNA Elements
  • Copyright 
    The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC-ND 4.0 International license.
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    Posted April 30, 2018.
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    Super-enhancers are transcriptionally more active and cell-type-specific than stretch enhancers
    Aziz Khan, Anthony Mathelier, Xuegong Zhang
    bioRxiv 310839; doi: https://doi.org/10.1101/310839
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    Super-enhancers are transcriptionally more active and cell-type-specific than stretch enhancers
    Aziz Khan, Anthony Mathelier, Xuegong Zhang
    bioRxiv 310839; doi: https://doi.org/10.1101/310839

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