Document Detail


De novo DNA methylation of endogenous retroviruses is shaped by KRAB-ZFPs/KAP1 and ESET.
MedLine Citation:
PMID:  23293284     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Endogenous retroviruses (ERVs) undergo de novo DNA methylation during the first few days of mammalian embryogenesis, although the factors that control the targeting of this process are largely unknown. We asked whether KAP1 (KRAB-associated protein 1) is involved in this mechanism because of its previously defined role in maintaining the silencing of ERVs through the histone methyltransferase ESET and histone H3 lysine 9 trimethylation. Here, we demonstrate that introduced ERV sequences are sufficient to direct rapid de novo methylation of a flanked promoter in embryonic stem (ES) cells. This mechanism requires the presence of an ERV sequence-recognizing KRAB zinc-finger protein (ZFP) and both KAP1 and ESET. Furthermore, this process can also take place on a strong cellular promoter and leads to methylation signatures that are subsequently maintained in vivo throughout embryogenesis. Finally, we show that methylation of ERVs residing in the genome is affected by knockout of KAP1 in early embryos. KRAB-ZFPs, KAP1 and ESET are thus likely to be responsible for the early embryonic instatement of stable epigenetic marks at ERV-containing loci.
Authors:
Helen M Rowe; Marc Friedli; Sandra Offner; Sonia Verp; Daniel Mesnard; Julien Marquis; Tugce Aktas; Didier Trono
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Development (Cambridge, England)     Volume:  140     ISSN:  1477-9129     ISO Abbreviation:  Development     Publication Date:  2013 Feb 
Date Detail:
Created Date:  2013-01-07     Completed Date:  2013-03-07     Revised Date:  2013-03-27    
Medline Journal Info:
Nlm Unique ID:  8701744     Medline TA:  Development     Country:  England    
Other Details:
Languages:  eng     Pagination:  519-29     Citation Subset:  IM    
Affiliation:
School of Life Sciences and Frontiers in Genetics Program, Ecole Polytechnique Fédérale de Lausanne (EPFL), Lausanne, Switzerland.
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MeSH Terms
Descriptor/Qualifier:
Animals
Animals, Genetically Modified
DNA Methylation*
DNA, Viral / genetics,  metabolism*
Embryo, Mammalian / cytology,  metabolism,  virology
Embryonic Stem Cells / cytology,  metabolism,  virology
Endogenous Retroviruses / enzymology,  genetics,  metabolism*
Gene Expression Regulation, Developmental
Gene Knockout Techniques
Gene Silencing
Gene Transfer Techniques
Genetic Vectors / genetics,  metabolism
HEK293 Cells
Histone-Lysine N-Methyltransferase / genetics,  metabolism*
Histones / genetics,  metabolism
Humans
Lentivirus / genetics,  metabolism
Mice
Nuclear Proteins / genetics,  metabolism*
Promoter Regions, Genetic
Repressor Proteins / genetics,  metabolism*
Transcriptome
Transfection
Grant Support
ID/Acronym/Agency:
268721//European Research Council
Chemical
Reg. No./Substance:
0/DNA, Viral; 0/Histones; 0/Nuclear Proteins; 0/Repressor Proteins; 0/Trim28 protein, mouse; EC 2.1.1.43/Histone-Lysine N-Methyltransferase; EC 2.1.1.43/SETDB1 protein, mouse

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