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A genome-scale map of DNA methylation turnover identifies site-specific dependencies of DNMT and TET activity.


ABSTRACT: DNA methylation is considered a stable epigenetic mark, yet methylation patterns can vary during differentiation and in diseases such as cancer. Local levels of DNA methylation result from opposing enzymatic activities, the rates of which remain largely unknown. Here we developed a theoretical and experimental framework enabling us to infer methylation and demethylation rates at 860,404 CpGs in mouse embryonic stem cells. We find that enzymatic rates can vary as much as two orders of magnitude between CpGs with identical steady-state DNA methylation. Unexpectedly, de novo and maintenance methylation activity is reduced at transcription factor binding sites, while methylation turnover is elevated in transcribed gene bodies. Furthermore, we show that TET activity contributes substantially more than passive demethylation to establishing low methylation levels at distal enhancers. Taken together, our work unveils a genome-scale map of methylation kinetics, revealing highly variable and context-specific activity for the DNA methylation machinery.

SUBMITTER: Ginno PA 

PROVIDER: S-EPMC7260214 | biostudies-literature | 2020 May

REPOSITORIES: biostudies-literature

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A genome-scale map of DNA methylation turnover identifies site-specific dependencies of DNMT and TET activity.

Ginno Paul Adrian PA   Gaidatzis Dimos D   Feldmann Angelika A   Hoerner Leslie L   Imanci Dilek D   Burger Lukas L   Zilbermann Frederic F   Peters Antoine H F M AHFM   Edenhofer Frank F   Smallwood Sébastien A SA   Krebs Arnaud R AR   Schübeler Dirk D  

Nature communications 20200529 1


DNA methylation is considered a stable epigenetic mark, yet methylation patterns can vary during differentiation and in diseases such as cancer. Local levels of DNA methylation result from opposing enzymatic activities, the rates of which remain largely unknown. Here we developed a theoretical and experimental framework enabling us to infer methylation and demethylation rates at 860,404 CpGs in mouse embryonic stem cells. We find that enzymatic rates can vary as much as two orders of magnitude b  ...[more]

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