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  • 1
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    Germline DNA demethylation dynamics and imprint erasure through 5-hydroxymethylcytosine (2012)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 2012-12-12
    Description: Mouse primordial germ cells (PGCs) undergo sequential epigenetic changes and genome-wide DNA demethylation to reset the epigenome for totipotency. Here, we demonstrate that erasure of CpG methylation (5mC) in PGCs occurs via conversion to 5-hydroxymethylcytosine (5hmC), driven by high levels of TET1 and TET2. Global conversion to 5hmC initiates asynchronously among PGCs at embryonic day (E) 9.5 to E10.5 and accounts for the unique process of imprint erasure. Mechanistically, 5hmC enrichment is followed by its protracted decline thereafter at a rate consistent with replication-coupled dilution. The conversion to 5hmC is an important component of parallel redundant systems that drive comprehensive reprogramming in PGCs. Nonetheless, we identify rare regulatory elements that escape systematic DNA demethylation in PGCs, providing a potential mechanistic basis for transgenerational epigenetic inheritance.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3847602/" 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/PMC3847602/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Hackett, Jamie A -- Sengupta, Roopsha -- Zylicz, Jan J -- Murakami, Kazuhiro -- Lee, Caroline -- Down, Thomas A -- Surani, M Azim -- 079249/Wellcome Trust/United Kingdom -- 083089/Wellcome Trust/United Kingdom -- 083563/Wellcome Trust/United Kingdom -- 092096/Wellcome Trust/United Kingdom -- RG44593/Wellcome Trust/United Kingdom -- RG49135/Wellcome Trust/United Kingdom -- New York, N.Y. -- Science. 2013 Jan 25;339(6118):448-52. doi: 10.1126/science.1229277. Epub 2012 Dec 6.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Wellcome Trust/Cancer Research UK Gurdon Institute, University of Cambridge, Cambridge CB2 1QN, UK.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/23223451" target="_blank"〉PubMed〈/a〉
    Keywords: 5-Methylcytosine/metabolism ; Animals ; CpG Islands ; Cytosine/*analogs & derivatives/metabolism ; *DNA Methylation ; DNA-Binding Proteins/genetics/metabolism ; Embryo, Mammalian/*metabolism ; Embryonic Development ; *Epigenesis, Genetic ; Female ; *Genomic Imprinting ; Germ Cells/*metabolism ; Germ Layers/cytology ; Male ; Mice ; Promoter Regions, Genetic ; Proto-Oncogene Proteins/genetics/metabolism ; RNA-Binding Proteins/genetics
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
    Published by American Association for the Advancement of Science (AAAS)
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  • 2
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    Development. Programming the X chromosome (2004)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 2004-01-31
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Hajkova, Petra -- Surani, M Azim -- New York, N.Y. -- Science. 2004 Jan 30;303(5658):633-4.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Wellcome Trust Cancer Research UK Gurdon Institute, University of Cambridge, Cambridge CB2 1QR, UK.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/14752149" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Chromosomes, Mammalian/physiology ; *Dosage Compensation, Genetic ; Embryo, Mammalian/*physiology ; *Embryo, Nonmammalian ; *Embryonic and Fetal Development ; Female ; *Gene Expression Regulation, Developmental ; Genes, Homeobox ; Genomic Imprinting ; Histones/metabolism ; Male ; Methylation ; Placenta/*physiology ; Pluripotent Stem Cells/physiology ; Polycomb Repressive Complex 2 ; Proteins/metabolism ; RNA, Long Noncoding ; RNA, Untranslated/metabolism ; Repressor Proteins/metabolism ; X Chromosome/*physiology
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
    Published by American Association for the Advancement of Science (AAAS)
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  • 3
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    Germ cell specification in mice (2007)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 2007-04-21
    Description: Specification of germ cells in mice occurs relatively late in embryonic development. It is initiated by signals that induce expression of Blimp1, a key regulator of the germ cell, in a few epiblast cells of early postimplantation embryos. Blimp1 represses the incipient somatic program in these cells and promotes progression toward the germ cell fate. Blimp1 may also have a role in the maintenance of early germ cell characteristics by ensuring their escape from the somatic fate as well as possible reversion to pluripotent stem cells.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Hayashi, Katsuhiko -- de Sousa Lopes, Susana M Chuva -- Surani, M Azim -- Wellcome Trust/United Kingdom -- New York, N.Y. -- Science. 2007 Apr 20;316(5823):394-6.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Wellcome Trust Cancer Research UK Gurdon Institute, University of Cambridge, Tennis Court Road, Cambridge CB2 1QN, UK.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/17446386" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Cell Differentiation ; Cell Lineage ; Embryo, Mammalian/*cytology/physiology ; Embryonic Development ; Epigenesis, Genetic ; Gene Expression Regulation, Developmental ; Germ Cells/*cytology ; Mice ; Phenotype ; Pluripotent Stem Cells/cytology ; Protein Methyltransferases/genetics/physiology ; Repressor Proteins/physiology ; Transcription Factors/physiology ; Transcription, Genetic
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
    Published by American Association for the Advancement of Science (AAAS)
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  • 4
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    Genome-wide reprogramming in the mouse germ line entails the base excision repair pathway (2010)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 2010-07-03
    Description: Genome-wide active DNA demethylation in primordial germ cells (PGCs), which reprograms the epigenome for totipotency, is linked to changes in nuclear architecture, loss of histone modifications, and widespread histone replacement. Here, we show that DNA demethylation in the mouse PGCs is mechanistically linked to the appearance of single-stranded DNA (ssDNA) breaks and the activation of the base excision repair (BER) pathway, as is the case in the zygote where the paternal pronucleus undergoes active DNA demethylation shortly after fertilization. Whereas BER might be triggered by deamination of a methylcytosine (5mC), cumulative evidence indicates other mechanisms in germ cells. We demonstrate that DNA repair through BER represents a core component of genome-wide DNA demethylation in vivo and provides a mechanistic link to the extensive chromatin remodeling in developing PGCs.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3863715/" 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/PMC3863715/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Hajkova, Petra -- Jeffries, Sean J -- Lee, Caroline -- Miller, Nigel -- Jackson, Stephen P -- Surani, M Azim -- 083089/Wellcome Trust/United Kingdom -- 11224/Cancer Research UK/United Kingdom -- A11224/Cancer Research UK/United Kingdom -- G0800784/Medical Research Council/United Kingdom -- MC_U120092689/Medical Research Council/United Kingdom -- Wellcome Trust/United Kingdom -- New York, N.Y. -- Science. 2010 Jul 2;329(5987):78-82. doi: 10.1126/science.1187945.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Wellcome Trust-Cancer Research U.K. Gurdon Institute of Cancer and Developmental Biology, University of Cambridge, Tennis Court Road, Cambridge CB2 1QN, UK. petra.hajkova@csc.mrc.ac.uk〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20595612" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Benzamides/pharmacology ; Cell Nucleus/metabolism ; Chromatin/metabolism ; *Chromatin Assembly and Disassembly ; *DNA Breaks, Single-Stranded ; *DNA Methylation ; *DNA Repair/drug effects ; DNA-Binding Proteins/metabolism ; Embryo, Mammalian/metabolism ; Embryonic Development ; Enzyme Inhibitors/pharmacology ; *Epigenesis, Genetic ; Female ; *Genome ; Germ Cells/*metabolism ; Histones/metabolism ; Indoles/pharmacology ; Male ; Mice ; Poly Adenosine Diphosphate Ribose/metabolism ; Zygote/drug effects/metabolism
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
    Published by American Association for the Advancement of Science (AAAS)
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  • 5
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    Development of gynogenetic eggs in the mouse: implications for parthenogenetic embryos (1983)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 1983-12-02
    Description: Mouse eggs with different genetic constitutions were prepared by micromanipulation of fertilized diploids and triploids. The diploid gynogenones, activated by the male gamete which was then removed, developed at best to about the 25-somite stage as did the genetically similar diploid parthenogenones stimulated to develop in the complete absence of the male gamete. The failure of development to term in both cases may be due to homozygosity and does not appear to be due to a lack of extragenetic contribution from spermatozoa.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Surani, M A -- Barton, S C -- New York, N.Y. -- Science. 1983 Dec 2;222(4627):1034-6.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/6648518" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Cell Division ; Cytoplasm/physiology ; Embryo Implantation ; Embryo Transfer ; Embryo, Mammalian/*physiology ; Female ; Genes, Lethal ; Homozygote ; Male ; Mice ; Mice, Inbred BALB C ; Mice, Inbred C57BL ; *Parthenogenesis ; Spermatozoa/physiology
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
    Published by American Association for the Advancement of Science (AAAS)
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