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

Michael B. Stadler, Rabih Murr, Lukas Burger, Robert Ivanek, Florian Lienert, Anne Schöler, Christiane Wirbelauer, Edward J. Oakeley, Dimos Gaidatzis, Vijay K. Tiwari, Dirk Schübeler

Research output: Chapter in Book/Report/Conference proceedingChapter

739 Citations (Scopus)

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.
Original languageEnglish
Title of host publicationNature
Pages490-495
Number of pages6
DOIs
Publication statusPublished - 22 Dec 2011

Publication series

NameNature
Volume480

Fingerprint

Nucleic Acid Regulatory Sequences
Methylation
DNA
Stem Cells
Deoxyribonuclease I
Cytosine
DNA Methylation
Epigenomics
Base Pairing
Chromatin
Hypersensitivity
Transcription Factors
Genome

Cite this

Stadler, M. B., Murr, R., Burger, L., Ivanek, R., Lienert, F., Schöler, A., ... Schübeler, D. (2011). DNA-binding factors shape the mouse methylome at distal regulatory regions. In Nature (pp. 490-495). (Nature; Vol. 480). https://doi.org/10.1038/nature10716
Stadler, Michael B. ; Murr, Rabih ; Burger, Lukas ; Ivanek, Robert ; Lienert, Florian ; Schöler, Anne ; Wirbelauer, Christiane ; Oakeley, Edward J. ; Gaidatzis, Dimos ; Tiwari, Vijay K. ; Schübeler, Dirk. / DNA-binding factors shape the mouse methylome at distal regulatory regions. Nature. 2011. pp. 490-495 (Nature).
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Stadler, MB, Murr, R, Burger, L, Ivanek, R, Lienert, F, Schöler, A, Wirbelauer, C, Oakeley, EJ, Gaidatzis, D, Tiwari, VK & Schübeler, D 2011, DNA-binding factors shape the mouse methylome at distal regulatory regions. in Nature. Nature, vol. 480, pp. 490-495. https://doi.org/10.1038/nature10716

DNA-binding factors shape the mouse methylome at distal regulatory regions. / Stadler, Michael B.; Murr, Rabih; Burger, Lukas; Ivanek, Robert; Lienert, Florian; Schöler, Anne; Wirbelauer, Christiane; Oakeley, Edward J.; Gaidatzis, Dimos; Tiwari, Vijay K.; Schübeler, Dirk.

Nature. 2011. p. 490-495 (Nature; Vol. 480).

Research output: Chapter in Book/Report/Conference proceedingChapter

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Stadler MB, Murr R, Burger L, Ivanek R, Lienert F, Schöler A et al. DNA-binding factors shape the mouse methylome at distal regulatory regions. In Nature. 2011. p. 490-495. (Nature). https://doi.org/10.1038/nature10716