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The Kruppel-associated box repressor domain can trigger de novo promoter methylation during mouse early embryogenesis

Wiznerowicz, Maciej ; Jakobsson, Johan LU orcid ; Szulc, Jolanta ; Liao, Shunyao ; Quazzola, Alexandra ; Beermann, Friedrich ; Aebischer, Patrick and Trono, Didier (2007) In Journal of Biological Chemistry 282(47). p.41-34535
Abstract

The Krüppel-associated box (KRAB) domain is a transcriptional repression module responsible for the DNA binding-dependent gene silencing activity of hundreds of vertebrate zinc finger proteins. We previously exploited KRAB-mediated repression within the context of a tet repressor-KRAB fusion protein and of lentiviral vectors to create a method of external gene control. We demonstrated that with this system transcriptional silencing was fully reversible in cell culture as well as in vivo. Here we reveal that, in sharp contrast, KRAB-mediated repression results in irreversible gene silencing through promoter DNA methylation if it acts during the first few days of mouse development.

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author
; ; ; ; ; ; and
publishing date
type
Contribution to journal
publication status
published
keywords
Animals, Carrier Proteins, DNA Methylation, Embryonic Development, Gene Silencing, Lentivirus, Mice, Nuclear Proteins, Promoter Regions, Genetic, Protein Structure, Tertiary, Repressor Proteins, Transcription, Genetic, Journal Article, Research Support, Non-U.S. Gov't
in
Journal of Biological Chemistry
volume
282
issue
47
pages
7 pages
publisher
American Society for Biochemistry and Molecular Biology
external identifiers
  • pmid:17893143
  • scopus:36348930084
ISSN
0021-9258
DOI
10.1074/jbc.M705898200
language
English
LU publication?
no
id
38911131-0ef1-4618-aaa9-0d37a9cf52cb
date added to LUP
2016-11-23 14:42:26
date last changed
2024-04-19 13:18:03
@article{38911131-0ef1-4618-aaa9-0d37a9cf52cb,
  abstract     = {{<p>The Krüppel-associated box (KRAB) domain is a transcriptional repression module responsible for the DNA binding-dependent gene silencing activity of hundreds of vertebrate zinc finger proteins. We previously exploited KRAB-mediated repression within the context of a tet repressor-KRAB fusion protein and of lentiviral vectors to create a method of external gene control. We demonstrated that with this system transcriptional silencing was fully reversible in cell culture as well as in vivo. Here we reveal that, in sharp contrast, KRAB-mediated repression results in irreversible gene silencing through promoter DNA methylation if it acts during the first few days of mouse development.</p>}},
  author       = {{Wiznerowicz, Maciej and Jakobsson, Johan and Szulc, Jolanta and Liao, Shunyao and Quazzola, Alexandra and Beermann, Friedrich and Aebischer, Patrick and Trono, Didier}},
  issn         = {{0021-9258}},
  keywords     = {{Animals; Carrier Proteins; DNA Methylation; Embryonic Development; Gene Silencing; Lentivirus; Mice; Nuclear Proteins; Promoter Regions, Genetic; Protein Structure, Tertiary; Repressor Proteins; Transcription, Genetic; Journal Article; Research Support, Non-U.S. Gov't}},
  language     = {{eng}},
  month        = {{11}},
  number       = {{47}},
  pages        = {{41--34535}},
  publisher    = {{American Society for Biochemistry and Molecular Biology}},
  series       = {{Journal of Biological Chemistry}},
  title        = {{The Kruppel-associated box repressor domain can trigger de novo promoter methylation during mouse early embryogenesis}},
  url          = {{http://dx.doi.org/10.1074/jbc.M705898200}},
  doi          = {{10.1074/jbc.M705898200}},
  volume       = {{282}},
  year         = {{2007}},
}