Dataset Information


DNA binding factors shape the mouse methylome at distal regulatory regions [strand-specific-RNA-seq]

ABSTRACT: To gain insights into the interplay between DNA methylation and gene regulation we generated a basepair resolution reference map of the mouse methylome in stem cells and neurons. High genome coverage allowed for a novel quantitative analysis of local methylation states, which identified Low Methylated Regions (LMR) with an average methylation of 30%. These regions are evolutionary conserved, reside outside of CpG islands and distal to promoters. They represent regulatory regions evidenced by their DNaseI hypersensitivity and chromatin marks of enhancer elements. LMRs are occupied by transcription factors (TF) and their reduced methylation requires TF binding while introduction of TF binding sites creates LMRs de novo. This dependency on TF activity is further evident when comparing the methylomes of embryonic stem cells and derived neuronal cells. LMRs present in both cell types are occupied by broadly expressed factors, while LMRs present at only one state are occupied by cell-type specific TFs. Methylome data can thus enhance the prediction of occupied TF binding sites and identification of active regulatory regions genome-wide. Our study provides reference methylomes for the mouse at two cell states, identifies a novel and highly dynamic feature of the epigenome that defines distal regulatory elements and shows that transcription factor binding dynamically shapes mammalian methylomes. Strand specific expression profiling by high throughput sequencing.

ORGANISM(S): Mus musculus  

SUBMITTER: Anne Scholer   Dimos Gaidatzis  Robert Ivanek  Michael B Stadler  Rabih Murr  Lukas Burger  Dirk Schuebeler  Dirk Schubeler  Vijay Tiwari  Florian Lienert  Edward J Oakeley 

PROVIDER: E-GEOD-31385 | ArrayExpress | 2011-12-15



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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, pres  ...[more]

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