Publication Date:
2011-12-16
Description:
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.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Stadler, Michael B -- Murr, Rabih -- Burger, Lukas -- Ivanek, Robert -- Lienert, Florian -- Scholer, Anne -- van Nimwegen, Erik -- Wirbelauer, Christiane -- Oakeley, Edward J -- Gaidatzis, Dimos -- Tiwari, Vijay K -- Schubeler, Dirk -- England -- Nature. 2011 Dec 14;480(7378):490-5. doi: 10.1038/nature10716.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Friedrich Miescher Institute for Biomedical Research, Maulbeerstrasse 66, 4058 Basel, Switzerland.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/22170606" target="_blank"〉PubMed〈/a〉
Keywords:
Animals
;
Cell Differentiation
;
CpG Islands
;
Cytosine/*metabolism
;
*DNA Methylation
;
DNA-Binding Proteins/*metabolism
;
Embryonic Stem Cells/cytology
;
*Epigenomics
;
Mice
;
Neurons/cytology
;
Promoter Regions, Genetic/genetics
;
Protein Binding
;
Stem Cells/cytology
;
Transcription Factors/metabolism
Print ISSN:
0028-0836
Electronic ISSN:
1476-4687
Topics:
Biology
,
Chemistry and Pharmacology
,
Medicine
,
Natural Sciences in General
,
Physics
Permalink