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In embryonic stem cells, ZFP57/KAP1 recognize a methylated hexanucleotide to affect chromatin and DNA methylation of imprinting control regions.

Type of publication Peer-reviewed
Publikationsform Original article (peer-reviewed)
Publication date 2011
Author Quenneville Simon, Verde Gaetano, Corsinotti Andrea, Kapopoulou Adamandia, Jakobsson Johan, Offner Sandra, Baglivo Ilaria, Pedone Paolo V, Grimaldi Giovanna, Riccio Andrea, Trono Didier,
Project KRAB/KAP1 epigenetic regulation in the control of memory and emotional traits: from mice to humans.
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Original article (peer-reviewed)

Journal Molecular cell
Volume (Issue) 44(3)
Page(s) 361 - 72
Title of proceedings Molecular cell
DOI 10.1016/j.molcel.2011.08.032

Abstract

The maintenance of H3K9 and DNA methylation at imprinting control regions (ICRs) during early embryogenesis is key to the regulation of imprinted genes. Here, we reveal that ZFP57, its cofactor KAP1, and associated effectors bind selectively to the H3K9me3-bearing, DNA-methylated allele of ICRs in ES cells. KAP1 deletion induces a loss of heterochromatin marks at ICRs, whereas deleting ZFP57 or DNMTs leads to ICR DNA demethylation. Accordingly, we find that ZFP57 and KAP1 associated with DNMTs and hemimethylated DNA-binding NP95. Finally, we identify the methylated TGCCGC hexanucleotide as the motif that is recognized by ZFP57 in all ICRs and in several tens of additional loci, several of which are at least ZFP57-dependently methylated in ES cells. These results significantly advance our understanding of imprinting and suggest a general mechanism for the protection of specific loci against the wave of DNA demethylation that affects the mammalian genome during early embryogenesis.
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