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- W2139538863 abstract "Abstract Genome-wide demethylation and remethylation of DNA during early embryogenesis is essential for development. Imprinted germline differentially methylated domains (gDMDs) established by sex-specific methylation in either male or female germ cells, must escape these dynamic changes and sustain precise inheritance of both methylated and unmethylated parental alleles. To identify other, gDMD-like sequences with the same epigenetic inheritance properties, we used a modified embryonic stem (ES) cell line that emulates the early embryonic demethylation and remethylation waves. Transient DNMT1 suppression revealed gDMD-like sequences requiring continuous DNMT1 activity to sustain a highly methylated state. Remethylation of these sequences was also compromised in vivo in a mouse model of transient DNMT1 loss in the preimplantation embryo. These novel regions, possessing heritable epigenetic features similar to imprinted-gDMDs are required for normal physiological and developmental processes and when disrupted are associated with disorders such as cancer and autism spectrum disorders. This study presents new perspectives on DNA methylation heritability during early embryo development that extend beyond conventional imprinted-gDMDs." @default.
- W2139538863 created "2016-06-24" @default.
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- W2139538863 date "2015-01-10" @default.
- W2139538863 modified "2023-09-26" @default.
- W2139538863 title "Transient DNMT1 suppression reveals hidden heritable marks in the genome" @default.
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- W2139538863 doi "https://doi.org/10.1093/nar/gku1386" @default.
- W2139538863 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/4330356" @default.
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