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Cell. 2014 May 8;157(4):979-991. doi: 10.1016/j.cell.2014.04.017.

Programming and inheritance of parental DNA methylomes in mammals.

Author information

1
CAS Key Laboratory of Genome Sciences and Information, Chinese Academy of Sciences, Beijing 100101, China.
2
University of Chinese Academy of Sciences, Beijing 100049, China.
3
Model Animal Research Center, Nanjing University, Nanjing 210061, China.
4
Department of Chemistry and Institute for Biophysical Dynamics, The University of Chicago, Chicago, IL 60637, USA.
5
Biodynamic Optical Imaging Center, College of Life Sciences, Peking University, Beijing 100871, China.
6
Laboratory of Disease Genomics and Individualized Medicine Beijing Institute of Genomics, Chinese Academy of Sciences, Beijing 100101, China.
7
Institute of Zoology, Chinese Academy of Sciences, Beijing 100101, China.
8
Woods Hole Oceanographic Institution, MA 02543, USA.
#
Contributed equally

Erratum in

  • Cell. 2014 Jun 19;157(7):1735.

Abstract

The reprogramming of parental methylomes is essential for embryonic development. In mammals, paternal 5-methylcytosines (5mCs) have been proposed to be actively converted to oxidized bases. These paternal oxidized bases and maternal 5mCs are believed to be passively diluted by cell divisions. By generating single-base resolution, allele-specific DNA methylomes from mouse gametes, early embryos, and primordial germ cell (PGC), as well as single-base-resolution maps of oxidized cytosine bases for early embryos, we report the existence of 5hmC and 5fC in both maternal and paternal genomes and find that 5mC or its oxidized derivatives, at the majority of demethylated CpGs, are converted to unmodified cytosines independent of passive dilution from gametes to four-cell embryos. Therefore, we conclude that paternal methylome and at least a significant proportion of maternal methylome go through active demethylation during embryonic development. Additionally, all the known imprinting control regions (ICRs) were classified into germ-line or somatic ICRs.

PMID:
24813617
PMCID:
PMC4096154
DOI:
10.1016/j.cell.2014.04.017
[Indexed for MEDLINE]
Free PMC Article

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