Functional cis-regulatory modules encoded by mouse-specific endogenous retrovirus
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 co...
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Veröffentlicht in: | Nature communications 2017-03, Vol.8 (1), p.14550-14550, Article 14550 |
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Sprache: | eng |
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Zusammenfassung: | 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.
The gene-battery model posits transposable elements (TEs) may be
cis
-regulatory elements to control gene expression. Here, mouse-specific TEs are shown as binding sites for multiple collaborating transcription factors in embryonic stem cells, and act as
cis
-regulatory modules in synergistic fashion. |
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ISSN: | 2041-1723 2041-1723 |
DOI: | 10.1038/ncomms14550 |