Journal
NATURE
Volume 480, Issue 7378, Pages 490-495Publisher
NATURE PUBLISHING GROUP
DOI: 10.1038/nature10716
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Funding
- EMBO
- Marie Curie International Incoming fellowship
- Novartis Research Foundation
- European Union (NoE) [FP7-HEALTH-2010-257082]
- European Research Council (ERC EpiGePlas)
- SNF
- Swiss initiative in Systems Biology
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Methylation of cytosines is an essential epigenetic modification in mammalian genomes, yet the rules that govern methylation patterns remain largely elusive. To gain insights into this process, we generated base-pair-resolution mouse methylomes in stem cells and neuronal progenitors. Advanced quantitative analysis identified low-methylated regions (LMRs) with an average methylation of 30%. These represent CpG-poor distal regulatory regions as evidenced by location, DNase I hypersensitivity, presence of enhancer chromatin marks and enhancer activity in reporter assays. LMRs are occupied by DNA-binding factors and their binding is necessary and sufficient to create LMRs. A comparison of neuronal and stem-cell methylomes confirms this dependency, as cell-type-specific LMRs are occupied by cell-type-specific transcription factors. This study provides methylome references for the mouse and shows that DNA-binding factors locally influence DNA methylation, enabling the identification of active regulatory regions.
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