Publication Date:
2014-08-01
Description:
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.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4178976/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉 〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4178976/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Smith, Zachary D -- Chan, Michelle M -- Humm, Kathryn C -- Karnik, Rahul -- Mekhoubad, Shila -- Regev, Aviv -- Eggan, Kevin -- Meissner, Alexander -- 1P50HG006193-01/HG/NHGRI NIH HHS/ -- 5DP1OD003958/OD/NIH HHS/ -- P01 GM099117/GM/NIGMS NIH HHS/ -- P01GM099117/GM/NIGMS NIH HHS/ -- P50 HG006193/HG/NHGRI NIH HHS/ -- U01 ES017155/ES/NIEHS NIH HHS/ -- Howard Hughes Medical Institute/ -- England -- Nature. 2014 Jul 31;511(7511):611-5. doi: 10.1038/nature13581. Epub 2014 Jul 23.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉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]. ; 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]. ; 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]. ; 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. ; 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. ; 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. ; 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.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25079558" target="_blank"〉PubMed〈/a〉
Keywords:
Animals
;
Blastocyst/*metabolism
;
Cell Line
;
CpG Islands/physiology
;
DNA/metabolism
;
*DNA Methylation
;
Embryonic Stem Cells
;
Female
;
Gene Expression Regulation, Developmental
;
Humans
;
Male
;
Mice
;
Mice, Inbred C57BL
Print ISSN:
0028-0836
Electronic ISSN:
1476-4687
Topics:
Biology
,
Chemistry and Pharmacology
,
Medicine
,
Natural Sciences in General
,
Physics
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