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

Research output: Contribution to journalArticle

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.

Details

Authors
  • Maciej Wiznerowicz
  • Johan Jakobsson
  • Jolanta Szulc
  • Shunyao Liao
  • Alexandra Quazzola
  • Friedrich Beermann
  • Patrick Aebischer
  • Didier Trono
External organisations
  • Swiss Federal Institute of Technology
Research areas and keywords

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
Original languageEnglish
Pages (from-to)34535-41
Number of pages7
JournalJournal of Biological Chemistry
Volume282
Issue number47
Publication statusPublished - 2007 Nov 23
Publication categoryResearch
Peer-reviewedYes
Externally publishedYes