Germline DNA Demethylation Dynamics and Imprint Erasure Through 5-Hydroxymethylcytosine
Wellcome/MRC Cambridge Stem Cell Institute · University of Cambridge · +3 more institutions
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…
Citation impact
- FWCI
- 36.27
- Percentile
- 100%
- References
- 27
Authors
7- JAJamie A. Hackett
Wellcome/MRC Cambridge Stem Cell Institute, University of Cambridge, The Gurdon Institute, Wellcome Trust, Medical Research Council
- RSRoopsha SenguptaCorresponding
Wellcome/MRC Cambridge Stem Cell Institute, University of Cambridge, The Gurdon Institute, Wellcome Trust, Medical Research Council
- JJJan J ŻyliczCorresponding
Wellcome/MRC Cambridge Stem Cell Institute, University of Cambridge, The Gurdon Institute, Wellcome Trust, Medical Research Council
- KMKazuhiro MurakamiCorresponding
Wellcome/MRC Cambridge Stem Cell Institute, University of Cambridge, The Gurdon Institute, Wellcome Trust, Medical Research Council
- CLCaroline Lee
Wellcome/MRC Cambridge Stem Cell Institute, University of Cambridge, The Gurdon Institute, Wellcome Trust, Medical Research Council
Topics & keywords
- 5-Hydroxymethylcytosine
- DNA demethylation
- Reprogramming
- Biology
- DNA methylation
- Epigenetics
- Epigenome
- Germline