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Series GSE63417 Query DataSets for GSE63417
Status Public on Dec 22, 2014
Title Genome-wide bisulfite sequencing in zygotes identifies demethylation targets and maps the contribution of TET3 oxidation
Organism Mus musculus
Experiment type Methylation profiling by high throughput sequencing
Summary Fertilization triggers a global erasure of 5-methylcytosine from paternal DNA as part of extensive epigenetic reprogramming during the transition from gametic specialization to totipotency. This active removal has been shown to involve oxidation by TET3, but the targeting of this pathway and the wider context of demethylation remain poorly understood. We optimized a novel technique for whole-genome bisulfite sequencing and applied it to wild-type and TET3-deficient zygotes, using SNPs to access paternal alleles. As the great majority of sperm-contributed methylation lies outside the CpG islands (CGIs) and promoters analysed to date, these genome-wide methylation profiles allow paternal methylation trajectories in the zygote to be comprehensively examined for the first time. This global view revealed that in addition to pervasive loss of methylation from intergenic sequences and most repetitive elements, 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 the early embryo. Our data maps the primary contribution of oxidative demethylation to a subset of gene bodies and single-copy intergenic sequences, and implicates the action of redundant pathways at many loci. We further uncover a novel function for TET3 in protection from de novo methylation at CGIs and promoters. This work adds new breadth to our understanding of the molecular events involved in reprogramming gametic identity following fertilization.
Overall design Three independent collections of zygotes were performed for each genotype (control and TET3 deletion), giving a total of 225 control and 237 TET3 deletion zygotes, of which 120 and 129 were derived from 129S2/SvHsd studs for control and TET3 samples, respectively. Zygotes were pooled and whole-genome bisulfite libraries were prepared using a post-bisulfite adaptor tagging strategy optimized from (Miura et al. Nucleic Acids Research 2012, 40:e136)
Contributor(s) Peat JR, Dean W, Clark SJ, Krueger F, Smallwood SA, Ficz G, Kim JK, Marioni JC, Hore TA, Reik W
Citation(s) 25497087
Submission date Nov 18, 2014
Last update date Mar 19, 2019
Contact name Felix Krueger
Organization name The Babraham Institute
Department Bioinformatics
Street address Babraham Hall
City Cambridge
ZIP/Postal code CB22 3AT
Country United Kingdom
Platforms (1)
GPL13112 Illumina HiSeq 2000 (Mus musculus)
Samples (2)
GSM1548411 Control Zygotes
GSM1548412 TET3 Deletion Zygotes
BioProject PRJNA267699
SRA SRP050005

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Supplementary file Size Download File type/resource
GSE63417_RAW.tar 365.6 Mb (http)(custom) TAR (of TXT)
Raw data are available in SRA
Processed data provided as supplementary file

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