Scientific Publications

DNA methylation dynamics of the human preimplantation embryo.

Publication TypeJournal Article
AuthorsSmith, ZD, Chan MM, Humm KC, Karnik R., Mekhoubad S., Regev A., Eggan K., and Meissner A.
AbstractIn 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.
Year of Publication2014
JournalNature
Volume511
Issue7511
Pages611-5
Date Published (YYYY/MM/DD)2014/07/31
ISSN Number0028-0836
DOI10.1038/nature13581
PubMedhttp://www.ncbi.nlm.nih.gov/pubmed/25079558?dopt=Abstract