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

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, Ava Hughes, Barak A. Cohen and Ting Wang ()
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Vasavi Sundaram: Washington University School of Medicine
Mayank N. K. Choudhary: 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
Manishi Pandey: Washington University School of Medicine
Brett Maricque: 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

Nature Communications, 2017, vol. 8, issue 1, 1-12

Abstract: 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.

Date: 2017
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DOI: 10.1038/ncomms14550

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