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Integrative analysis reveals genomic and epigenomic signatures of super-enhancers and its constituents

View ORCID ProfileAziz Khan, Xuegong Zhang
doi: https://doi.org/10.1101/105262
Aziz Khan
1MOE Key Laboratory of Bioinformatics, Bioinformatics Division and Center for Synthetic and Systems Biology, TNLIST/Department of Automation, Tsinghua University, Beijing, 100084, China
2Centre for Molecular Medicine Norway (NCMM), Nordic EMBL Partnership, University of Oslo, 0349 Oslo, Norway
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  • ORCID record for Aziz Khan
Xuegong Zhang
1MOE Key Laboratory of Bioinformatics, Bioinformatics Division and Center for Synthetic and Systems Biology, TNLIST/Department of Automation, Tsinghua University, Beijing, 100084, China
3School of Life Sciences, Tsinghua University, Beijing, 100084, China
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Abstract

Background Super-enhancers are clusters of transcriptional enhancers densely occupied by the Mediators, transcription factors and chromatin regulators. They control the expression of cell identity genes and disease associated genes. Current studies demonstrated the possibility of multiple factors with important roles in super-enhancer formation; however, a systematic analysis to assess the relative importance of chromatin and sequence signatures of super-enhancers and their constituents remain unclear.

Results Here, we integrated diverse types of genomic and epigenomic datasets to identify key signatures of super-enhancers and their constituents and to investigate their relative importance. Through computational modelling, we found that Cdk8, Cdk9 and Smad3 as new key features of super-enhancers along with many known features such as H3K27ac. Comprehensive analysis of these features in embryonic stem cells and pro-B cells revealed their role in the super-enhancer formation and cellular identity. We also observed that super-enhancers are significantly GC-rich in contrast with typical enhancers. Further, we observed significant correlation among many cofactors at the constituents of super-enhancers.

Conclusions Our analysis and ranking of super-enhancer signatures can serve as a resource to further characterize and understand the formation of super-enhancers. Our observations are consistent with a cooperative or synergistic model underlying the interaction of super-enhancers and their constituents with numerous factors.

Footnotes

  • Author’s email address: aziz.khan{at}ncmm.uio.no; zhangxg{at}tsinghua.edu.cn

  • Abbreviations

    TFs
    Transcription Factors
    ChIP-seq
    Chromatin immune precipitation followed by high-throughput sequencing
    ESCs
    Embryonic Stem Cells
    SEs
    Super-enhancers
    TEs
    Typical enhancers
    TSS
    Transcription Start Site
    SNPs
    Single Nucleotide Polymorphisms
    GEO
    Gene Expression Omnibus
    GO
    Gene Ontology
  • 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 4.0 International license.
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    Posted December 27, 2017.
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    Integrative analysis reveals genomic and epigenomic signatures of super-enhancers and its constituents
    Aziz Khan, Xuegong Zhang
    bioRxiv 105262; doi: https://doi.org/10.1101/105262
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    Integrative analysis reveals genomic and epigenomic signatures of super-enhancers and its constituents
    Aziz Khan, Xuegong Zhang
    bioRxiv 105262; doi: https://doi.org/10.1101/105262

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