Format

Send to

Choose Destination
Cell Rep. 2014 Dec 24;9(6):1990-2000. doi: 10.1016/j.celrep.2014.11.034. Epub 2014 Dec 12.

Genome-wide bisulfite sequencing in zygotes identifies demethylation targets and maps the contribution of TET3 oxidation.

Author information

1
Epigenetics Programme, The Babraham Institute, Cambridge CB22 3AT, UK. Electronic address: julian.peat@babraham.ac.uk.
2
Epigenetics Programme, The Babraham Institute, Cambridge CB22 3AT, UK.
3
Bioinformatics Group, The Babraham Institute, Cambridge CB22 3AT, UK.
4
European Molecular Biology Laboratory-European Bioinformatics Institute (EMBL-EBI), Hinxton CB10 1SD, UK.
5
European Molecular Biology Laboratory-European Bioinformatics Institute (EMBL-EBI), Hinxton CB10 1SD, UK; Wellcome Trust Sanger Institute, Hinxton CB10 1SA, UK.
6
Epigenetics Programme, The Babraham Institute, Cambridge CB22 3AT, UK; Wellcome Trust Sanger Institute, Hinxton CB10 1SA, UK; Centre for Trophoblast Research, University of Cambridge, Cambridge CB2 3EG, UK. Electronic address: wolf.reik@babraham.ac.uk.

Abstract

Fertilization triggers global erasure of paternal 5-methylcytosine as part of epigenetic reprogramming during the transition from gametic specialization to totipotency. This involves oxidation by TET3, but our understanding of its targets and the wider context of demethylation is limited to a small fraction of the genome. We employed an optimized bisulfite strategy to generate genome-wide methylation profiles of control and TET3-deficient zygotes, using SNPs to access paternal alleles. This revealed that in addition to pervasive removal from intergenic sequences and most retrotransposons, gene bodies constitute a major target of zygotic demethylation. Methylation loss is associated with zygotic genome activation and at gene bodies is also linked to increased transcriptional noise in early development. Our data map the primary contribution of oxidative demethylation to a subset of gene bodies and intergenic sequences and implicate redundant pathways at many loci. Unexpectedly, we demonstrate that TET3 activity also protects certain CpG islands against methylation buildup.

PMID:
25497087
PMCID:
PMC4542306
DOI:
10.1016/j.celrep.2014.11.034
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for Elsevier Science Icon for PubMed Central
Loading ...
Support Center