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, Ting Wang

Research output: Contribution to journalArticlepeer-review

31 Scopus citations

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.

Original languageEnglish
Article number14550
JournalNature communications
Volume8
DOIs
StatePublished - Mar 28 2017

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