Germline DNA demethylation dynamics and imprint erasure through 5-hydroxymethylcytosine.
basic_science · Level V
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- Record sourced from PubMed, PMID 23223451.
- Also identified by DOI 10.1126/science.1229277 and PMC identifier 3847602.
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Abstract
Mouse primordial germ cells (PGCs) undergo sequential epigenetic changes and genome-wide DNA demethylation to reset the epigenome for totipotency. Here, we demonstrate that erasure of CpG methylation (5mC) in PGCs occurs via conversion to 5-hydroxymethylcytosine (5hmC), driven by high levels of TET1 and TET2. Global conversion to 5hmC initiates asynchronously among PGCs at embryonic day (E) 9.5 to E10.5 and accounts for the unique process of imprint erasure. Mechanistically, 5hmC enrichment is followed by its protracted decline thereafter at a rate consistent with replication-coupled dilution. The conversion to 5hmC is an important component of parallel redundant systems that drive comprehensive reprogramming in PGCs. Nonetheless, we identify rare regulatory elements that escape systematic DNA demethylation in PGCs, providing a potential mechanistic basis for transgenerational epigenetic inheritance.
Medical subject headings
- Cytosine
- DNA Methylation
- Embryo, Mammalian
- Epigenesis, Genetic
- Genomic Imprinting
- Germ Cells