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dc.contributor.authorSmith, Zachary D.en_US
dc.contributor.authorChan, Michelle M.en_US
dc.contributor.authorHumm, Kathryn C.en_US
dc.contributor.authorKarnik, Rahulen_US
dc.contributor.authorMekhoubad, Shilaen_US
dc.contributor.authorRegev, Aviven_US
dc.contributor.authorEggan, Kevinen_US
dc.contributor.authorMeissner, Alexanderen_US
dc.date.accessioned2015-02-02T15:31:34Z
dc.date.issued2014en_US
dc.identifier.citationSmith, Zachary D., Michelle M. Chan, Kathryn C. Humm, Rahul Karnik, Shila Mekhoubad, Aviv Regev, Kevin Eggan, and Alexander Meissner. 2014. “DNA methylation dynamics of the human preimplantation embryo.” Nature 511 (7511): 611-615. doi:10.1038/nature13581. http://dx.doi.org/10.1038/nature13581.en
dc.identifier.issn0028-0836en
dc.identifier.urihttp://nrs.harvard.edu/urn-3:HUL.InstRepos:13890592
dc.description.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 factors1-3. This comparatively static landscape dramatically contrasts the events of fertilization, where the paternal genome is globally reprogrammed. Paternal genome demethylation includes the majority of CpGs, though methylation is maintained at several notable features4-7. While these dynamics have been extensively characterized in the mouse, only limited observations are available in other mammals, and direct measurements are required to understand the extent to which early embryonic landscapes are conserved8-10. We present genome-scale DNA methylation maps of human preimplantation development and embryonic stem cell (ESC) derivation, confirming a transient state of global hypomethylation that includes most CpGs, while sites of persistent maintenance are primarily restricted to gene bodies. While most features share similar dynamics to mouse, maternally contributed methylation is divergently targeted to species-specific sets of CpG island (CGI) promoters that extend beyond known Imprint Control Regions (ICRs). Retrotransposon regulation is also highly diverse and transitions from maternally to embryonically expressed, species-specific 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.en
dc.language.isoen_USen
dc.relation.isversionofdoi:10.1038/nature13581en
dc.relation.hasversionhttp://www.ncbi.nlm.nih.gov/pmc/articles/PMC4178976/pdf/en
dash.licenseLAAen_US
dc.titleDNA methylation dynamics of the human preimplantation embryoen
dc.typeJournal Articleen_US
dc.description.versionVersion of Recorden
dc.relation.journalNatureen
dash.depositing.authorSmith, Zachary D.en_US
dc.date.available2015-02-02T15:31:34Z
dc.identifier.doi10.1038/nature13581*
dash.contributor.affiliatedMekhoubad, Shila
dash.contributor.affiliatedSmith, Zachary
dash.contributor.affiliatedKarnik, Rahul
dash.contributor.affiliatedMeissner, Alexander
dash.contributor.affiliatedEggan, Kevin


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