Article

Contribution of intragenic DNA methylation in mouse gametic DNA methylomes to establish oocyte-specific heritable marks.

Department of BioScience, Tokyo University of Agriculture, Tokyo, Japan.
PLoS Genetics (impact factor: 8.69). 01/2012; 8(1):e1002440. DOI:10.1371/journal.pgen.1002440
Source: PubMed

ABSTRACT Genome-wide dynamic changes in DNA methylation are indispensable for germline development and genomic imprinting in mammals. Here, we report single-base resolution DNA methylome and transcriptome maps of mouse germ cells, generated using whole-genome shotgun bisulfite sequencing and cDNA sequencing (mRNA-seq). Oocyte genomes showed a significant positive correlation between mRNA transcript levels and methylation of the transcribed region. Sperm genomes had nearly complete coverage of methylation, except in the CpG-rich regions, and showed a significant negative correlation between gene expression and promoter methylation. Thus, these methylome maps revealed that oocytes and sperms are widely different in the extent and distribution of DNA methylation. Furthermore, a comparison of oocyte and sperm methylomes identified more than 1,600 CpG islands differentially methylated in oocytes and sperm (germline differentially methylated regions, gDMRs), in addition to the known imprinting control regions (ICRs). About half of these differentially methylated DNA sequences appear to be at least partially resistant to the global DNA demethylation that occurs during preimplantation development. In the absence of Dnmt3L, neither methylation of most oocyte-methylated gDMRs nor intragenic methylation was observed. There was also genome-wide hypomethylation, and partial methylation at particular retrotransposons, while maintaining global gene expression, in oocytes. Along with the identification of the many Dnmt3L-dependent gDMRs at intragenic regions, the present results suggest that oocyte methylation can be divided into 2 types: Dnmt3L-dependent methylation, which is required for maternal methylation imprinting, and Dnmt3L-independent methylation, which might be essential for endogenous retroviral DNA silencing. The present data provide entirely new perspectives on the evaluation of epigenetic markers in germline cells.

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Keywords

2 types
 
cDNA sequencing
 
DNA methylation
 
Dnmt3L-dependent methylation
 
Dnmt3L-independent methylation
 
gene expression
 
genomic imprinting
 
germline development
 
global DNA demethylation
 
global gene expression
 
intragenic methylation
 
maternal methylation imprinting
 
oocyte methylation
 
partial methylation
 
preimplantation development
 
promoter methylation
 
significant negative correlation
 
significant positive correlation
 
transcriptome maps
 
whole-genome shotgun bisulfite sequencing