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Tytuł pozycji:

Proviral silencing in embryonic stem cells requires the histone methyltransferase ESET.

Tytuł :
Proviral silencing in embryonic stem cells requires the histone methyltransferase ESET.
Index Terms :
Animals
Cell Line
DNA (Cytosine-5-)-Methyltransferase/deficiency
DNA (Cytosine-5-)-Methyltransferase/genetics
DNA (Cytosine-5-)-Methyltransferase/metabolism
DNA Methylation/genetics
Embryonic Stem Cells/enzymology
Embryonic Stem Cells/metabolism
Embryonic Stem Cells/virology
Endogenous Retroviruses/genetics
Fibroblasts
Gene Deletion
Gene Silencing
Histone-Lysine N-Methyltransferase/deficiency
Histone-Lysine N-Methyltransferase/genetics
Histone-Lysine N-Methyltransferase/metabolism
Mice
Nuclear Proteins/metabolism
Protein Methyltransferases/deficiency
Protein Methyltransferases/genetics
Protein Methyltransferases/metabolism
Proviruses/genetics
Repressor Proteins/metabolism
Journal Article
Źródło :
Nature
Wydawca :
Nature Publishing Group 2010-05-21T07:22:23Z 2010-05-21T07:22:23Z 2010-02-17
Dodane szczegóły :
眞貝, 洋一
Matsui, Toshiyuki
Leung, Danny
Miyashita, Hiroki
Maksakova, Irina A
Miyachi, Hitoshi
Kimura, Hiroshi
Tachibana, Makoto
Lorincz, Matthew C
Shinkai, Yoichi
Typ dokumentu :
Zasób elektroniczny
URL :
http://hdl.handle.net/2433/112675">http://hdl.handle.net/2433/112675
10.1038/nature08858
Dostępność :
© 2010 Nature Publishing Group
Pozostałe numery :
YJ@ oai:repository.kulib.kyoto-u.ac.jp:2433/112675
0028-0836
AA00752384
Nature
464
7290
927
931
20164836
816440463
Źródło wspomagające :
From OAIster®, provided by the OCLC Cooperative.
Numer akcesji :
edsoai.ocn816440463
Zasób elektroniczny
Endogenous retroviruses (ERVs), retrovirus-like elements with long terminal repeats, are widely dispersed in the euchromatic compartment in mammalian cells, comprising approximately 10% of the mouse genome. These parasitic elements are responsible for >10% of spontaneous mutations. Whereas DNA methylation has an important role in proviral silencing in somatic and germ-lineage cells, an additional DNA-methylation-independent pathway also functions in embryonal carcinoma and embryonic stem (ES) cells to inhibit transcription of the exogenous gammaretrovirus murine leukaemia virus (MLV). Notably, a recent genome-wide study revealed that ERVs are also marked by histone H3 lysine 9 trimethylation (H3K9me3) and H4K20me3 in ES cells but not in mouse embryonic fibroblasts. However, the role that these marks have in proviral silencing remains unexplored. Here we show that the H3K9 methyltransferase ESET (also called SETDB1 or KMT1E) and the Krüppel-associated box (KRAB)-associated protein 1 (KAP1, also called TRIM28) are required for H3K9me3 and silencing of endogenous and introduced retroviruses specifically in mouse ES cells. Furthermore, whereas ESET enzymatic activity is crucial for HP1 binding and efficient proviral silencing, the H4K20 methyltransferases Suv420h1 and Suv420h2 are dispensable for silencing. Notably, in DNA methyltransferase triple knockout (Dnmt1(-/-)Dnmt3a(-/-)Dnmt3b(-/-)) mouse ES cells, ESET and KAP1 binding and ESET-mediated H3K9me3 are maintained and ERVs are minimally derepressed. We propose that a DNA-methylation-independent pathway involving KAP1 and ESET/ESET-mediated H3K9me3 is required for proviral silencing during the period early in embryogenesis when DNA methylation is dynamically reprogrammed.

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