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Maintenance of DNA methylation in embryonic stem cells depends on the histone H3K9 methyltransferases (Dnmt3ab KO RNA-Seq)


ABSTRACT: During mammalian development DNA methylation patterns need to be reset in primordial germ cells (PGC) and preimplantation embryos. However, many retro-transposons and imprinted genes are resistant to such global epigenetic reprogramming via hitherto undefined mechanisms. Here, we report that some of these sequences are immune to widespread erasure of DNA methylation in the mouse embryonic stem cells (mESCs) lacking de novo DNA methyltransferases. Persistence of DNA methylation at these loci in mESCs depends on the histone H3K9 methyltransferase Setdb1, as deletion of Setdb1 results in reduction of H3K9me3 and DNA methylation levels concomitant with an increase in 5-hydroxymethylation (5hmC). In addition, depletion of H3K9 methyltransferase G9a leads to genome-wide reduction of DNA methylation but to a lesser extent at the above sequences. Taken together, these data reveal that Setdb1 ensures the fidelity of DNA methylation at specific loci in mESCs, which may reflect mechanisms functioning in vivo during key developmental stages. Examination of gene expression in 2 cell types by RNA-seq.

ORGANISM(S): Mus musculus

SUBMITTER: Ulrich Wagner 

PROVIDER: E-GEOD-47883 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Publications

Regulation of DNA methylation turnover at LTR retrotransposons and imprinted loci by the histone methyltransferase Setdb1.

Leung Danny D   Du Tingting T   Wagner Ulrich U   Xie Wei W   Lee Ah Young AY   Goyal Preeti P   Li Yujing Y   Szulwach Keith E KE   Jin Peng P   Lorincz Matthew C MC   Ren Bing B  

Proceedings of the National Academy of Sciences of the United States of America 20140422 18


During mammalian development, DNA methylation patterns need to be reset in primordial germ cells (PGCs) and preimplantation embryos. However, many LTR retrotransposons and imprinted genes are impervious to such global epigenetic reprogramming via hitherto undefined mechanisms. Here, we report that a subset of such genomic regions are resistant to widespread erasure of DNA methylation in mouse embryonic stem cells (mESCs) lacking the de novo DNA methyltransferases (Dnmts) Dnmt3a and Dnmt3b. Intri  ...[more]

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