title: DNA methylation dynamics of the human preimplantation embryo.
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.
authors: 1] Broad Institute of MIT and Harvard, Cambridge, Massachusetts 02142, USA [2] Harvard Stem Cell Institute, Cambridge, Massachusetts 02138, USA [3] Department of Stem Cell and Regenerative Biology, Harvard University, Cambridge, Massachusetts 02138, USA [4] Department of Molecular and Cellular Biology, Harvard University, Cambridge, Massachusetts 02138, USA [5].
authors: Zachary D
authors: ZD
authors: Smith
authors: 1] Broad Institute of MIT and Harvard, Cambridge, Massachusetts 02142, USA [2] Computational and Systems Biology Program, Massachusetts Institute of Technology, Cambridge, Massachusetts 02142, USA [3].
authors: Michelle M
authors: MM
authors: Chan
authors: 1] Department of Stem Cell and Regenerative Biology, Harvard University, Cambridge, Massachusetts 02138, USA [2] Division of Reproductive Endocrinology &Infertility, Department of Obstetrics &Gynecology, Beth Israel Deaconess Medical Center, Boston, Massachusetts 02215, USA [3] Obstetrics, Gynecology, and Reproductive Biology, Harvard Medical School, Boston, Massachusetts 02215, USA [4] Boston IVF, Waltham, Massachusetts 02451, USA [5] Howard Hughes Medical Institute, Massachusetts Institute of Technology, Cambridge, Massachusetts 02142, USA [6].
authors: Kathryn C
authors: KC
authors: Humm
authors: 1] Broad Institute of MIT and Harvard, Cambridge, Massachusetts 02142, USA [2] Harvard Stem Cell Institute, Cambridge, Massachusetts 02138, USA [3] Department of Stem Cell and Regenerative Biology, Harvard University, Cambridge, Massachusetts 02138, USA.
authors: Rahul
authors: R
authors: Karnik
authors: 1] Department of Stem Cell and Regenerative Biology, Harvard University, Cambridge, Massachusetts 02138, USA [2] Department of Molecular and Cellular Biology, Harvard University, Cambridge, Massachusetts 02138, USA.
authors: Shila
authors: S
authors: Mekhoubad
authors: 1] Broad Institute of MIT and Harvard, Cambridge, Massachusetts 02142, USA [2] Howard Hughes Medical Institute, Massachusetts Institute of Technology, Cambridge, Massachusetts 02142, USA [3] Massachusetts Institute of Technology, Cambridge, Massachusetts 02142, USA.
authors: Aviv
authors: A
authors: Regev
authors: 1] Broad Institute of MIT and Harvard, Cambridge, Massachusetts 02142, USA [2] Harvard Stem Cell Institute, Cambridge, Massachusetts 02138, USA [3] Department of Stem Cell and Regenerative Biology, Harvard University, Cambridge, Massachusetts 02138, USA [4] Department of Molecular and Cellular Biology, Harvard University, Cambridge, Massachusetts 02138, USA [5] Howard Hughes Medical Institute, Harvard University, Cambridge, Massachusetts 02138, USA.
authors: Kevin
authors: K
authors: Eggan
authors: 1] Broad Institute of MIT and Harvard, Cambridge, Massachusetts 02142, USA [2] Harvard Stem Cell Institute, Cambridge, Massachusetts 02138, USA [3] Department of Stem Cell and Regenerative Biology, Harvard University, Cambridge, Massachusetts 02138, USA.
authors: Alexander
authors: A
authors: Meissner
mesh_terms: D000818:Animals; D001755:Blastocyst / Q000378:metabolism*; D002460:Cell Line; D018899:CpG Islands / Q000502:physiology; D004247:DNA / Q000378:metabolism; D019175:DNA Methylation; D053595:Embryonic Stem Cells; D005260:Female; D018507:Gene Expression Regulation, Developmental; D006801:Humans; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL
chemical_list: D004247:DNA