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DNA-binding factors shape the mouse methylome at distal regulatory regions

Stadler, Michael, Murr, Rabih, Wirbelauer, Christiane, Burger, Lukas, Ivanek, Robert, Lienert, Florian, Schoeler, Anne, Oakeley, Edward James, Gaidatzis, Dimosthenis, Tiwari, Vijay and Schuebeler, Dirk (2011) DNA-binding factors shape the mouse methylome at distal regulatory regions. Nature, 480 (7378). pp. 490-495. ISSN 0028-0836


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 matter, we generated basepair resolution mouse methylomes in stem cells and neuronal progenitor cells. Advanced quantitative analysis identified Low Methylated Regions (LMRs) with an average methylation of 30%. These represent CpG-poor distal regulatory regions as evidenced by their location, DNaseI hypersensitivity and the presence of enhancer chromatin marks. LMRs are occupied by transcription factors and we show experimentally that transcription factor binding is necessary and sufficient to create LMRs. A comparison of the neuronal and stem cell methylomes confirms this dependency as cell type-specific LMRs are occupied by cell type specific transcription factors. In addition to providing an important epigenome reference for the mouse model our study discovers and explains a previously unrecognized, dynamic and regulated feature of mammalian methylomes that can predict transcription factor binding and identify active regulatory regions.

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Date Deposited: 13 Oct 2015 13:15
Last Modified: 13 Oct 2015 13:15