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Functional cis-regulatory modules encoded by mouse-specific endogenous retrovirus

Author

Listed:
  • Vasavi Sundaram

    (Washington University School of Medicine
    Center for Genome Sciences and Systems Biology, Washington University School of Medicine)

  • Mayank N. K. Choudhary

    (Washington University School of Medicine
    Center for Genome Sciences and Systems Biology, Washington University School of Medicine)

  • Erica Pehrsson

    (Center for Genome Sciences and Systems Biology, Washington University School of Medicine)

  • Xiaoyun Xing

    (Center for Genome Sciences and Systems Biology, Washington University School of Medicine)

  • Christopher Fiore

    (Washington University School of Medicine
    Center for Genome Sciences and Systems Biology, Washington University School of Medicine)

  • Manishi Pandey

    (Washington University School of Medicine
    Center for Genome Sciences and Systems Biology, Washington University School of Medicine)

  • Brett Maricque

    (Washington University School of Medicine
    Center for Genome Sciences and Systems Biology, Washington University School of Medicine)

  • Methma Udawatta

    (Center for Genome Sciences and Systems Biology, Washington University School of Medicine)

  • Duc Ngo

    (Center for Genome Sciences and Systems Biology, Washington University School of Medicine)

  • Yujie Chen

    (Center for Genome Sciences and Systems Biology, Washington University School of Medicine)

  • Asia Paguntalan

    (Center for Genome Sciences and Systems Biology, Washington University School of Medicine)

  • Tammy Ray

    (Center for Genome Sciences and Systems Biology, Washington University School of Medicine)

  • Ava Hughes

    (Center for Genome Sciences and Systems Biology, Washington University School of Medicine)

  • Barak A. Cohen

    (Center for Genome Sciences and Systems Biology, Washington University School of Medicine)

  • Ting Wang

    (Center for Genome Sciences and Systems Biology, Washington University School of Medicine)

Abstract

Cis-regulatory modules contain multiple transcription factor (TF)-binding sites and integrate the effects of each TF to control gene expression in specific cellular contexts. Transposable elements (TEs) are uniquely equipped to deposit their regulatory sequences across a genome, which could also contain cis-regulatory modules that coordinate the control of multiple genes with the same regulatory logic. We provide the first evidence of mouse-specific TEs that encode a module of TF-binding sites in mouse embryonic stem cells (ESCs). The majority (77%) of the individual TEs tested exhibited enhancer activity in mouse ESCs. By mutating individual TF-binding sites within the TE, we identified a module of TF-binding motifs that cooperatively enhanced gene expression. Interestingly, we also observed the same motif module in the in silico constructed ancestral TE that also acted cooperatively to enhance gene expression. Our results suggest that ancestral TE insertions might have brought in cis-regulatory modules into the mouse genome.

Suggested Citation

  • Vasavi Sundaram & Mayank N. K. Choudhary & Erica Pehrsson & Xiaoyun Xing & Christopher Fiore & Manishi Pandey & Brett Maricque & Methma Udawatta & Duc Ngo & Yujie Chen & Asia Paguntalan & Tammy Ray & , 2017. "Functional cis-regulatory modules encoded by mouse-specific endogenous retrovirus," Nature Communications, Nature, vol. 8(1), pages 1-12, April.
  • Handle: RePEc:nat:natcom:v:8:y:2017:i:1:d:10.1038_ncomms14550
    DOI: 10.1038/ncomms14550
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    Cited by:

    1. Jia Lu & Xiaoyi Cao & Sheng Zhong, 2018. "A likelihood approach to testing hypotheses on the co-evolution of epigenome and genome," PLOS Computational Biology, Public Library of Science, vol. 14(12), pages 1-28, December.

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