De novo DNA methylation of endogenous retroviruses is shaped by KRAB-ZFPs/KAP1 and ESET.
Details
Serval ID
serval:BIB_A5538752C3D0
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
De novo DNA methylation of endogenous retroviruses is shaped by KRAB-ZFPs/KAP1 and ESET.
Journal
Development (Cambridge, England)
Publication state
Published
Issued date
02/2013
Volume
140
Number
3
Pages
519-529
Language
english
Abstract
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.
Keywords
Animals, HEK293 Cells, Humans, Mice, Gene Transfer Techniques, Promoter Regions, Genetic, Transcriptome, Gene Expression Regulation, Developmental, Tripartite Motif-Containing Protein 28, Nuclear Proteins/genetics/*metabolism, Repressor Proteins/genetics/*metabolism, *DNA Methylation, Animals, Genetically Modified, DNA, Viral/genetics/*metabolism, Embryo, Mammalian/cytology/metabolism/virology, Embryonic Stem Cells/cytology/metabolism/virology, Endogenous Retroviruses/enzymology/genetics/*metabolism, Gene Knockout Techniques, Gene Silencing, Genetic Vectors/genetics/metabolism, Histone-Lysine N-Methyltransferase/genetics/*metabolism, Histones/genetics/metabolism, Lentivirus/genetics/metabolism, Transfection
Pubmed
Create date
19/02/2020 12:23
Last modification date
19/06/2020 5:26