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J Biol Chem. 2007 Nov 23;282(47):34535-41. Epub 2007 Sep 24.

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

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  • 1School of Life Sciences, "Frontiers in Genetics" National Center for Competence in Research, Ecole Polytechnique Fédérale de Lausanne, Lausanne, Switzerland.

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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