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
