Interplay of TRIM28 and DNA methylation in controlling human endogenous retroelements
- Priscilla Turelli1,
- Nathaly Castro-Diaz1,
- Flavia Marzetta1,
- Adamandia Kapopoulou1,
- Charlene Raclot1,
- Julien Duc1,
- Vannary Tieng2,
- Simon Quenneville1 and
- Didier Trono1,3
- ↵* Corresponding author; email: didier.trono{at}epfl.ch
Abstract
Reverse transcription-derived sequences account for at least half of the human genome. Although these retroelements are formidable motors of evolution, they can occasionally cause disease, and accordingly are inactivated during early embryogenesis through epigenetic mechanisms. In the mouse, at least for endogenous retroviruses, important mediators of this process are the tetrapod-specific KRAB-containing zinc finger proteins (KRAB-ZFPs) and their cofactor TRIM28. The present study demonstrates that KRAB/TRIM28-mediated regulation is responsible for controlling a very broad range of human-specific endogenous retroelements (EREs) in human embryonic stem (ES) cells and that it exerts, as a consequence, a marked effect on the transcriptional dynamics of these cells. It further reveals reciprocal dependence between TRIM28 recruitment at specific families of EREs and DNA methylation. It finally points to the importance of persistent TRIM28-mediated control of ERE transcriptional impact beyond their presumed inactivation by DNA methylation.
- Received January 21, 2014.
- Accepted May 28, 2014.
- Published by Cold Spring Harbor Laboratory Press
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