AI Article Synopsis
- DNA methylation is an important epigenetic marker that changes during cell differentiation and diseases like cancer, but the rates of methylation and demethylation remain largely uncharted.
- We created a framework to analyze methylation rates at over 860,000 CpGs in mouse embryonic stem cells, revealing significant variability in enzymatic activity even at CpGs with similar overall methylation levels.
- Our findings indicate reduced methylation at transcription factor binding sites and higher turnover in gene bodies, while a specific enzyme (TET) plays a crucial role in maintaining low methylation at enhancer regions.
Article 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.
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| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7260214 | PMC |
| http://dx.doi.org/10.1038/s41467-020-16354-x | DOI Listing |
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