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Endogenous retroviruses co-opted as divergently transcribed regulatory elements shape the regulatory landscape of embryonic stem cells

View ORCID ProfileStylianos Bakoulis, View ORCID ProfileRobert Krautz, View ORCID ProfileNicolas Alcaraz, View ORCID ProfileMarco Salvatore, View ORCID ProfileRobin Andersson
doi: https://doi.org/10.1101/2021.06.11.448013
Stylianos Bakoulis
1The Bioinformatics Centre, Department of Biology, University of Copenhagen, 2200, Copenhagen, Denmark
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Robert Krautz
1The Bioinformatics Centre, Department of Biology, University of Copenhagen, 2200, Copenhagen, Denmark
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Nicolas Alcaraz
1The Bioinformatics Centre, Department of Biology, University of Copenhagen, 2200, Copenhagen, Denmark
2Novo Nordisk Foundation Center for Protein Research (CPR), University of Copenhagen, 2200, Copenhagen, Denmark
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Marco Salvatore
1The Bioinformatics Centre, Department of Biology, University of Copenhagen, 2200, Copenhagen, Denmark
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Robin Andersson
1The Bioinformatics Centre, Department of Biology, University of Copenhagen, 2200, Copenhagen, Denmark
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  • For correspondence: robin@binf.ku.dk
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Abstract

Transposable elements are an abundant source of transcription factor binding sites and favorable genomic integration may lead to their recruitment by the host genome for gene regulatory functions. However, it is unclear how frequent co-option of transposable elements as regulatory elements is, to which regulatory programs they contribute and how they compare to regulatory elements devoid of transposable elements. Here, we report a transcription initiation-centric, in-depth characterization of the transposon-derived regulatory landscape of mouse embryonic stem cells. We demonstrate that a substantial number of transposable elements, in particular endogenous retroviral elements, carry open chromatin regions that are divergently transcribed into unstable RNAs in a cell-type specific manner, and that these elements contribute to a sizable proportion of active enhancers and gene promoters. We further show that transposon subfamilies contribute differently and distinctly to the pluripotency regulatory program through their repertoires of transcription factor binding sites, shedding light on the formation of regulatory programs and the origins of regulatory elements.

Competing Interest Statement

The authors have declared no competing interest.

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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-ND 4.0 International license.
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Posted January 06, 2022.
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Endogenous retroviruses co-opted as divergently transcribed regulatory elements shape the regulatory landscape of embryonic stem cells
Stylianos Bakoulis, Robert Krautz, Nicolas Alcaraz, Marco Salvatore, Robin Andersson
bioRxiv 2021.06.11.448013; doi: https://doi.org/10.1101/2021.06.11.448013
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Endogenous retroviruses co-opted as divergently transcribed regulatory elements shape the regulatory landscape of embryonic stem cells
Stylianos Bakoulis, Robert Krautz, Nicolas Alcaraz, Marco Salvatore, Robin Andersson
bioRxiv 2021.06.11.448013; doi: https://doi.org/10.1101/2021.06.11.448013

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