Oct 3, 2014

Maternal DNMT3A-dependent de novo methylation of the zygotic paternal genome inhibits gene expression in the early embryo

bioRxiv
Timothée PoisotMatthew C Lorincz

Abstract

De novo DNA methylation (DNAme) during mammalian spermatogenesis yields a densely methylated genome, with the exception of CpG islands (CGIs), which are hypomethylated in sperm. Following fertilization, the paternal genome undergoes widespread DNAme loss before the first S-phase. Paradoxically, recent mass spectrometry analysis revealed that a low level of de novo DNAme occurs exclusively on the zygotic paternal genome. However, the loci involved and impact on genic transcription was not addressed. Here, we employ allele-specific analysis of whole-genome bisulphite sequencing (WGBS) data and show that a number of genomic regions, including several dozen CGI promoters, are de novo methylated on the paternal genome in 2-cell embryos. A subset of these promoters maintains DNAme through development to the blastocyst stage. Consistent with zygotic paternal DNAme acquisition (PDA), many of these loci are hypermethylated in androgenetic blastocysts but hypomethylated in parthenogenetic blastocysts. Strikingly, PDA is lost following maternal deletion of Dnmt3a . Furthermore, a subset of promoters showing PDA which are normally transcribed from the paternal allele in blastocysts show premature transcription at the 4-cell stage in matern...Continue Reading

  • References
  • Citations

References

  • We're still populating references for this paper, please check back later.
  • References
  • Citations

Citations

  • This paper may not have been cited yet.

Mentioned in this Paper

Study
Theoretical Study
Anatomical Space Structure
Structure
Population Group
Entity - Organization
Communicable Diseases

Related Feeds

BioRxiv & MedRxiv Preprints

BioRxiv and MedRxiv are the preprint servers for biology and health sciences respectively, operated by Cold Spring Harbor Laboratory. Here are the latest preprint articles (which are not peer-reviewed) from BioRxiv and MedRxiv.