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      DNA methylation dynamics during epigenetic reprogramming in the germline and preimplantation embryos

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          Abstract

          Methylation of DNA is an essential epigenetic control mechanism in mammals. Messerschmidt et al. review the current understanding of epigenetic dynamics regulating the molecular processes that prepare the mammalian embryo for normal development.

          Abstract

          Methylation of DNA is an essential epigenetic control mechanism in mammals. During embryonic development, cells are directed toward their future lineages, and DNA methylation poses a fundamental epigenetic barrier that guides and restricts differentiation and prevents regression into an undifferentiated state. DNA methylation also plays an important role in sex chromosome dosage compensation, the repression of retrotransposons that threaten genome integrity, the maintenance of genome stability, and the coordinated expression of imprinted genes. However, DNA methylation marks must be globally removed to allow for sexual reproduction and the adoption of the specialized, hypomethylated epigenome of the primordial germ cell and the preimplantation embryo. Recent technological advances in genome-wide DNA methylation analysis and the functional description of novel enzymatic DNA demethylation pathways have provided significant insights into the molecular processes that prepare the mammalian embryo for normal development.

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          Most cited references167

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          Initial sequencing and analysis of the human genome.

          The human genome holds an extraordinary trove of information about human development, physiology, medicine and evolution. Here we report the results of an international collaboration to produce and make freely available a draft sequence of the human genome. We also present an initial analysis of the data, describing some of the insights that can be gleaned from the sequence.
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            Conversion of 5-methylcytosine to 5-hydroxymethylcytosine in mammalian DNA by MLL partner TET1.

            DNA cytosine methylation is crucial for retrotransposon silencing and mammalian development. In a computational search for enzymes that could modify 5-methylcytosine (5mC), we identified TET proteins as mammalian homologs of the trypanosome proteins JBP1 and JBP2, which have been proposed to oxidize the 5-methyl group of thymine. We show here that TET1, a fusion partner of the MLL gene in acute myeloid leukemia, is a 2-oxoglutarate (2OG)- and Fe(II)-dependent enzyme that catalyzes conversion of 5mC to 5-hydroxymethylcytosine (hmC) in cultured cells and in vitro. hmC is present in the genome of mouse embryonic stem cells, and hmC levels decrease upon RNA interference-mediated depletion of TET1. Thus, TET proteins have potential roles in epigenetic regulation through modification of 5mC to hmC.
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              DNA methylation: roles in mammalian development.

              DNA methylation is among the best studied epigenetic modifications and is essential to mammalian development. Although the methylation status of most CpG dinucleotides in the genome is stably propagated through mitosis, improvements to methods for measuring methylation have identified numerous regions in which it is dynamically regulated. In this Review, we discuss key concepts in the function of DNA methylation in mammals, stemming from more than two decades of research, including many recent studies that have elucidated when and where DNA methylation has a regulatory role in the genome. We include insights from early development, embryonic stem cells and adult lineages, particularly haematopoiesis, to highlight the general features of this modification as it participates in both global and localized epigenetic regulation.
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                Author and article information

                Journal
                Genes Dev
                Genes Dev
                GAD
                Genes & Development
                Cold Spring Harbor Laboratory Press
                0890-9369
                1549-5477
                15 April 2014
                : 28
                : 8
                : 812-828
                Affiliations
                [1 ]Developmental Epigenetics and Disease, Institute of Molecular and Cell Biology (IMCB), Agency for Science, Technology, and Research (A*STAR), 138673 Singapore,;
                [2 ]The Jackson Laboratory, Bar Harbor, Maine 04609, USA;
                [3 ]Mammalian Development, Institute of Medical Biology (IMB), A*STAR, 138648 Singapore
                Author notes
                [4 ]Corresponding author E-mail danielm@ 123456imcb.a-star.edu.sg
                Article
                8711660
                10.1101/gad.234294.113
                4003274
                24736841
                54e96489-54a8-4b22-b85c-843e8fd3ecf4
                © 2014 Messerschmidt et al.; Published by Cold Spring Harbor Laboratory Press

                This article is distributed exclusively by Cold Spring Harbor Laboratory Press for the first six months after the full-issue publication date (see http://genesdev.cshlp.org/site/misc/terms.xhtml). After six months, it is available under a Creative Commons License (Attribution-NonCommercial 4.0 International), as described at http://creativecommons.org/licenses/by-nc/4.0/.

                History
                Page count
                Pages: 17
                Categories
                5
                11
                23
                Review

                dna methylation,development,epigenetics,reprogramming
                dna methylation, development, epigenetics, reprogramming

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