You are here

Nature DOI:10.1038/nature13581

DNA methylation dynamics of the human preimplantation embryo.

Publication TypeJournal Article
Year of Publication2014
AuthorsSmith, ZD, Chan, MM, Humm, KC, Karnik, R, Mekhoubad, S, Regev, A, Eggan, K, Meissner, A
JournalNature
Volume511
Issue7511
Pages611-5
Date Published2014 Jul 31
ISSN1476-4687
KeywordsAnimals, Blastocyst, Cell Line, CpG Islands, DNA, DNA Methylation, Embryonic Stem Cells, Female, Gene Expression Regulation, Developmental, Humans, Male, Mice, Mice, Inbred C57BL
Abstract

In mammals, cytosine methylation is predominantly restricted to CpG dinucleotides and stably distributed across the genome, with local, cell-type-specific regulation directed by DNA binding factors. This comparatively static landscape is in marked contrast with the events of fertilization, during which the paternal genome is globally reprogrammed. Paternal genome demethylation includes the majority of CpGs, although methylation remains detectable at several notable features. These dynamics have been extensively characterized in the mouse, with only limited observations available in other mammals, and direct measurements are required to understand the extent to which early embryonic landscapes are conserved. We present genome-scale DNA methylation maps of human preimplantation development and embryonic stem cell derivation, confirming a transient state of global hypomethylation that includes most CpGs, while sites of residual maintenance are primarily restricted to gene bodies. Although most features share similar dynamics to those in mouse, maternally contributed methylation is divergently targeted to species-specific sets of CpG island promoters that extend beyond known imprint control regions. Retrotransposon regulation is also highly diverse, and transitions from maternally to embryonically expressed elements. Together, our data confirm that paternal genome demethylation is a general attribute of early mammalian development that is characterized by distinct modes of epigenetic regulation.

URLhttp://dx.doi.org/10.1038/nature13581
DOI10.1038/nature13581
Pubmed

http://www.ncbi.nlm.nih.gov/pubmed/25079558?dopt=Abstract

Alternate JournalNature
PubMed ID25079558
PubMed Central IDPMC4178976
Grant ListP01 GM099117 / GM / NIGMS NIH HHS / United States
5DP1OD003958 / OD / NIH HHS / United States
P01GM099117 / GM / NIGMS NIH HHS / United States
P50 HG006193 / HG / NHGRI NIH HHS / United States
/ / Howard Hughes Medical Institute / United States
1P50HG006193-01 / HG / NHGRI NIH HHS / United States
U01 ES017155 / ES / NIEHS NIH HHS / United States
DP1 OD003958 / OD / NIH HHS / United States