Loss of transcriptional control over endogenous retroelements during reprogramming to pluripotency.

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Version: Final published version
License: CC BY-NC 4.0
Serval ID
serval:BIB_92065EE1168B
Type
Article: article from journal or magazin.
Collection
Publications
Title
Loss of transcriptional control over endogenous retroelements during reprogramming to pluripotency.
Journal
Genome Research
Author(s)
Friedli M., Turelli P., Kapopoulou A., Rauwel B., Castro-Díaz N., Rowe H.M., Ecco G., Unzu C., Planet E., Lombardo A., Mangeat B., Wildhaber B.E., Naldini L., Trono D.
ISSN
1549-5469 (Electronic)
ISSN-L
1088-9051
Publication state
Published
Issued date
2014
Peer-reviewed
Oui
Volume
24
Number
8
Pages
1251-1259
Language
english
Notes
Publication types: Journal Article ; Research Support, Non-U.S. Gov't Publication Status: ppublish
Abstract
Endogenous retroelements (EREs) account for about half of the mouse or human genome, and their potential as insertional mutagens and transcriptional perturbators is suppressed by early embryonic epigenetic silencing. Here, we asked how ERE control is maintained during the generation of induced pluripotent stem cells (iPSCs), as this procedure involves profound epigenetic remodeling. We found that all EREs tested were markedly up-regulated during the reprogramming of either mouse embryonic fibroblasts, human CD34(+) cells, or human primary hepatocytes. At the iPSC stage, EREs of some classes were repressed, whereas others remained highly expressed, yielding a pattern somewhat reminiscent of that recorded in embryonic stem cells. However, variability persisted between individual iPSC clones in the control of specific ERE integrants. Both during reprogramming and in iPS cells, the up-regulation of specific EREs significantly impacted on the transcription of nearby cellular genes. While transcription triggered by specific ERE integrants at highly precise developmental stages may be an essential step toward obtaining pluripotent cells, the broad and unspecific unleashing of the repetitive genome observed here may contribute to the inefficiency of the reprogramming process and to the phenotypic heterogeneity of iPSCs.
Pubmed
Web of science
Open Access
Yes
Create date
21/02/2015 11:11
Last modification date
22/11/2022 15:45
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