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

Michael B. Stadler, Rabih Murr, Lukas Burger, Robert Ivanek, Florian Lienert, Anne Schöler, Erik van Nimwegen, Christiane Wirbelauer, Edward J. Oakeley, Dimos Gaidatzis, Vijay K. Tiwari and Dirk Schübeler ()
Additional contact information
Michael B. Stadler: Friedrich Miescher Institute for Biomedical Research, Maulbeerstrasse 66, 4058 Basel, Switzerland
Rabih Murr: Friedrich Miescher Institute for Biomedical Research, Maulbeerstrasse 66, 4058 Basel, Switzerland
Lukas Burger: Friedrich Miescher Institute for Biomedical Research, Maulbeerstrasse 66, 4058 Basel, Switzerland
Robert Ivanek: Friedrich Miescher Institute for Biomedical Research, Maulbeerstrasse 66, 4058 Basel, Switzerland
Florian Lienert: Friedrich Miescher Institute for Biomedical Research, Maulbeerstrasse 66, 4058 Basel, Switzerland
Anne Schöler: Friedrich Miescher Institute for Biomedical Research, Maulbeerstrasse 66, 4058 Basel, Switzerland
Erik van Nimwegen: Biozentrum of the University of Basel and Swiss Institute of Bioinformatics, Klingelbergstrasse 50–70, CH 4056, Basel, Switzerland
Christiane Wirbelauer: Friedrich Miescher Institute for Biomedical Research, Maulbeerstrasse 66, 4058 Basel, Switzerland
Edward J. Oakeley: Novartis Institutes for BioMedical Research, Biomarker Development, 4056 Basel, Switzerland
Dimos Gaidatzis: Friedrich Miescher Institute for Biomedical Research, Maulbeerstrasse 66, 4058 Basel, Switzerland
Vijay K. Tiwari: Friedrich Miescher Institute for Biomedical Research, Maulbeerstrasse 66, 4058 Basel, Switzerland
Dirk Schübeler: Friedrich Miescher Institute for Biomedical Research, Maulbeerstrasse 66, 4058 Basel, Switzerland

Nature, 2011, vol. 480, issue 7378, 490-495

Abstract: Abstract 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.

Date: 2011
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DOI: 10.1038/nature10716

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