The Kruppel-associated box repressor domain can trigger de novo promoter methylation during mouse early embryogenesis.
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.
Wiznerowicz
Maciej
M
School of Life Sciences, "Frontiers in Genetics" National Center for Competence in Research, Ecole Polytechnique Fédérale de Lausanne, Lausanne, Switzerland.
Jakobsson
Johan
J
Szulc
Jolanta
J
Liao
Shunyao
S
Quazzola
Alexandra
A
Beermann
Friedrich
F
Aebischer
Patrick
P
Trono
Didier
D
D000818:Animals; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism*; D019175:DNA Methylation; D047108:Embryonic Development / Q000502:physiology*; D020868:Gene Silencing / Q000502:physiology; D016086:Lentivirus; D051379:Mice; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism*; D011401:Promoter Regions, Genetic / Q000502:physiology*; D017434:Protein Structure, Tertiary / Q000235:genetics; D012097:Repressor Proteins / Q000235:genetics / Q000378:metabolism*; D014158:Transcription, Genetic / Q000502:physiology*
D002352:Carrier Proteins; D009687:Nuclear Proteins; D012097:Repressor Proteins; C486788:Zfp472 protein, mouse