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TRIM28 repression of retrotransposon-based enhancers is necessary to preserve transcriptional dynamics in embryonic stem cells

Rowe, Helen M. ; Kapopoulou, Adamandia ; Corsinotti, Andrea ; Fasching, Liana LU ; Macfarlan, Todd S. ; Tarabay, Yara ; Viville, Stephane ; Jakobsson, Johan LU orcid ; Pfaff, Samuel L. and Trono, Didier (2013) In Genome Research 23(3). p.452-461
Abstract
TRIM28 is critical for the silencing of endogenous retroviruses (ERVs) in embryonic stem (ES) cells. Here, we reveal that an essential impact of this process is the protection of cellular gene expression in early embryos from perturbation by cis-acting activators contained within these retroelements. In TRIM28-depleted ES cells, repressive chromatin marks at ERVs are replaced by histone modifications typical of active enhancers, stimulating transcription of nearby cellular genes, notably those harboring bivalent promoters. Correspondingly, ERV-derived sequences can repress or enhance expression from an adjacent promoter in transgenic embryos depending on their TRIM28 sensitivity in ES cells. TRIM28-mediated control of ERVs is therefore... (More)
TRIM28 is critical for the silencing of endogenous retroviruses (ERVs) in embryonic stem (ES) cells. Here, we reveal that an essential impact of this process is the protection of cellular gene expression in early embryos from perturbation by cis-acting activators contained within these retroelements. In TRIM28-depleted ES cells, repressive chromatin marks at ERVs are replaced by histone modifications typical of active enhancers, stimulating transcription of nearby cellular genes, notably those harboring bivalent promoters. Correspondingly, ERV-derived sequences can repress or enhance expression from an adjacent promoter in transgenic embryos depending on their TRIM28 sensitivity in ES cells. TRIM28-mediated control of ERVs is therefore crucial not just to prevent retrotransposition, but more broadly to safeguard the transcriptional dynamics of early embryos. (Less)
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; ; ; ; ; ; ; ; and
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Genome Research
volume
23
issue
3
pages
452 - 461
publisher
Cold Spring Harbor Laboratory Press (CSHL)
external identifiers
  • wos:000315806800005
  • scopus:84874626481
  • pmid:23233547
ISSN
1549-5469
DOI
10.1101/gr.147678.112
language
English
LU publication?
yes
id
558d3dc2-6375-4957-a042-6b8eeedf0893 (old id 3657224)
date added to LUP
2016-04-01 13:40:12
date last changed
2022-03-29 08:37:38
@article{558d3dc2-6375-4957-a042-6b8eeedf0893,
  abstract     = {{TRIM28 is critical for the silencing of endogenous retroviruses (ERVs) in embryonic stem (ES) cells. Here, we reveal that an essential impact of this process is the protection of cellular gene expression in early embryos from perturbation by cis-acting activators contained within these retroelements. In TRIM28-depleted ES cells, repressive chromatin marks at ERVs are replaced by histone modifications typical of active enhancers, stimulating transcription of nearby cellular genes, notably those harboring bivalent promoters. Correspondingly, ERV-derived sequences can repress or enhance expression from an adjacent promoter in transgenic embryos depending on their TRIM28 sensitivity in ES cells. TRIM28-mediated control of ERVs is therefore crucial not just to prevent retrotransposition, but more broadly to safeguard the transcriptional dynamics of early embryos.}},
  author       = {{Rowe, Helen M. and Kapopoulou, Adamandia and Corsinotti, Andrea and Fasching, Liana and Macfarlan, Todd S. and Tarabay, Yara and Viville, Stephane and Jakobsson, Johan and Pfaff, Samuel L. and Trono, Didier}},
  issn         = {{1549-5469}},
  language     = {{eng}},
  number       = {{3}},
  pages        = {{452--461}},
  publisher    = {{Cold Spring Harbor Laboratory Press (CSHL)}},
  series       = {{Genome Research}},
  title        = {{TRIM28 repression of retrotransposon-based enhancers is necessary to preserve transcriptional dynamics in embryonic stem cells}},
  url          = {{https://lup.lub.lu.se/search/files/3518081/4022922.pdf}},
  doi          = {{10.1101/gr.147678.112}},
  volume       = {{23}},
  year         = {{2013}},
}