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

Stadler, Michael B. and Murr, Rabih and Burger, Lukas and Ivanek, Robert and Lienert, Florian and Schöler, Anne and van Nimwegen, Erik and Wirbelauer, Christiane and Oakeley, Edward J. and Gaidatzis, Dimos and Tiwari, Vijay K. and Schübeler, Dirk. (2011) DNA-binding factors shape the mouse methylome at distal regulatory regions. Nature, Vol. 480, H. 7378. S. 490-495.

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Official URL: http://edoc.unibas.ch/dok/A6002722

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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.
Faculties and Departments:05 Faculty of Science > Departement Biozentrum > Computational & Systems Biology > Bioinformatics (van Nimwegen)
UniBasel Contributors:van Nimwegen, Erik
Item Type:Article, refereed
Bibsysno:Link to catalogue
Publisher:Macmillan
ISSN:0028-0836
Note:Publication type according to Uni Basel Research Database: Journal article
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Last Modified:11 Oct 2012 15:31
Deposited On:11 Oct 2012 15:18

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