Identification of a region of the DNMT1 methyltransferase that regulates the maintenance of genomic imprints.

Proceedings of the National Academy of Sciences of the United States of America
Ewa BorowczykJ Richard Chaillet

Abstract

Reprogramming of DNA methylation patterns during mammalian preimplantation development involves the concurrent maintenance of methylation on differentially methylated domains (DMDs) of imprinted genes and a marked reduction of global (non-DMD) genomic methylation. In the developing mammalian embryo, one allele of a DMD is unmethylated, and the opposite parental allele is methylated, having inherited this methylation from the parental gamete. The maintenance of DMDs is important for monoallelic imprinted gene expression and normal development of the embryo. Because the DNMT1 cytosine methyltransferase governs maintenance methylation in mammals, rearrangements of non-DMD, but not DMD methylation in preimplantation embryos suggest that the preimplantation DNMT1-dependent maintenance mechanism specifically targets DMD sequences. We explored this possibility using an engineered mouse ES cell line to screen for mutant DNMT1 proteins that protect against the loss of DMD and/or global (non-DMD) methylation in the absence of the wild-type endogenous DNMT1 methyltransferase. We identified DNMT1 mutants that were defective in maintenance of either DMD and/or non-DMD methylation. Among these, one mutant maintained non-DMD methylation but n...Continue Reading

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Citations

Nov 9, 2010·Oncogene·R E RugoB P Engelward
Jul 5, 2012·Briefings in Functional Genomics·Ruslan Strogantsev, Anne C Ferguson-Smith
Mar 9, 2011·Molecular and Cellular Biology·K Naga MohanJ Richard Chaillet
Apr 16, 2011·Differentiation; Research in Biological Diversity·Leonardo D'AiutoJ Richard Chaillet
Dec 19, 2013·Biochimica Et Biophysica Acta·Jamie R Weaver, Marisa S Bartolomei
Jan 13, 2015·Nucleic Acids Research·Serge McGrawJacquetta M Trasler
Sep 5, 2017·International Journal of Molecular Sciences·Hongliang LiuZekun Guo
Dec 14, 2018·Genes·Marthe LaisnéPierre-Antoine Defossez

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