Genome-wide Bisulfite Sequencing in Zygotes Identifies Demethylation Targets and Maps the Contribution of TET3 Oxidation

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...

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Main Authors:	Peat, Julian R., Dean, Wendy, Clark, Stephen J., Krueger, Felix, Smallwood, Sébastien A., Ficz, Gabriella, Kim, Jong Kyoung, Marioni, John C., Hore, Timothy A., Reik, Wolf
Format:	Online
Language:	English
Published:	Cell Press 2014
Online Access:	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4542306/

id	pubmed-4542306
recordtype	oai_dc
spelling	pubmed-45423062015-09-22 Genome-wide Bisulfite Sequencing in Zygotes Identifies Demethylation Targets and Maps the Contribution of TET3 Oxidation Peat, Julian R. Dean, Wendy Clark, Stephen J. Krueger, Felix Smallwood, Sébastien A. Ficz, Gabriella Kim, Jong Kyoung Marioni, John C. Hore, Timothy A. Reik, Wolf Report 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. Cell Press 2014-12-12 /pmc/articles/PMC4542306/ /pubmed/25497087 http://dx.doi.org/10.1016/j.celrep.2014.11.034 Text en © 2014 The Authors http://creativecommons.org/licenses/by-nc-nd/3.0/ This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/3.0/).
repository_type	Open Access Journal
institution_category	Foreign Institution
institution	US National Center for Biotechnology Information
building	NCBI PubMed
collection	Online Access
language	English
format	Online
author	Peat, Julian R. Dean, Wendy Clark, Stephen J. Krueger, Felix Smallwood, Sébastien A. Ficz, Gabriella Kim, Jong Kyoung Marioni, John C. Hore, Timothy A. Reik, Wolf
spellingShingle	Peat, Julian R. Dean, Wendy Clark, Stephen J. Krueger, Felix Smallwood, Sébastien A. Ficz, Gabriella Kim, Jong Kyoung Marioni, John C. Hore, Timothy A. Reik, Wolf Genome-wide Bisulfite Sequencing in Zygotes Identifies Demethylation Targets and Maps the Contribution of TET3 Oxidation
author_facet	Peat, Julian R. Dean, Wendy Clark, Stephen J. Krueger, Felix Smallwood, Sébastien A. Ficz, Gabriella Kim, Jong Kyoung Marioni, John C. Hore, Timothy A. Reik, Wolf
author_sort	Peat, Julian R.
title	Genome-wide Bisulfite Sequencing in Zygotes Identifies Demethylation Targets and Maps the Contribution of TET3 Oxidation
title_short	Genome-wide Bisulfite Sequencing in Zygotes Identifies Demethylation Targets and Maps the Contribution of TET3 Oxidation
title_full	Genome-wide Bisulfite Sequencing in Zygotes Identifies Demethylation Targets and Maps the Contribution of TET3 Oxidation
title_fullStr	Genome-wide Bisulfite Sequencing in Zygotes Identifies Demethylation Targets and Maps the Contribution of TET3 Oxidation
title_full_unstemmed	Genome-wide Bisulfite Sequencing in Zygotes Identifies Demethylation Targets and Maps the Contribution of TET3 Oxidation
title_sort	genome-wide bisulfite sequencing in zygotes identifies demethylation targets and maps the contribution of tet3 oxidation
description	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.
publisher	Cell Press
publishDate	2014
url	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4542306/
_version_	1613261646292058112

Genome-wide Bisulfite Sequencing in Zygotes Identifies Demethylation Targets and Maps the Contribution of TET3 Oxidation

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