title: DNA-binding factors shape the mouse methylome at distal regulatory regions.
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.
authors.affiliation: Friedrich Miescher Institute for Biomedical Research, Maulbeerstrasse 66, 4058 Basel, Switzerland.
authors.forename: Michael B
authors.initials: MB
authors.lastname: Stadler
authors.forename: Rabih
authors.initials: R
authors.lastname: Murr
authors.forename: Lukas
authors.initials: L
authors.lastname: Burger
authors.forename: Robert
authors.initials: R
authors.lastname: Ivanek
authors.forename: Florian
authors.initials: F
authors.lastname: Lienert
authors.forename: Anne
authors.initials: A
authors.lastname: Schöler
authors.forename: Erik
authors.initials: E
authors.lastname: van Nimwegen
authors.forename: Christiane
authors.initials: C
authors.lastname: Wirbelauer
authors.forename: Edward J
authors.initials: EJ
authors.lastname: Oakeley
authors.forename: Dimos
authors.initials: D
authors.lastname: Gaidatzis
authors.forename: Vijay K
authors.initials: VK
authors.lastname: Tiwari
authors.forename: Dirk
authors.initials: D
authors.lastname: Schübeler
mesh_terms: D000818:Animals; D002454:Cell Differentiation; D018899:CpG Islands; D003596:Cytosine / Q000378:metabolism*; D019175:DNA Methylation; D004268:DNA-Binding Proteins / Q000378:metabolism*; D053595:Embryonic Stem Cells / Q000166:cytology; D057890:Epigenomics; D051379:Mice; D009474:Neurons / Q000166:cytology; D011401:Promoter Regions, Genetic / Q000235:genetics; D011485:Protein Binding; D013234:Stem Cells / Q000166:cytology; D014157:Transcription Factors / Q000378:metabolism
chemical_list: D004268:DNA-Binding Proteins; D014157:Transcription Factors; D003596:Cytosine