DNA-binding Factors Shape the Mouse Methylome at Distal Regulatory Regions

Overview

Journal Nature

Specialty Science

Date 2011 Dec 16

PMID 22170606

Citations 795

Authors

Michael B Stadler

Rabih Murr

Lukas Burger

Robert Ivanek

Florian Lienert

Anne Scholer

Erik van Nimwegen

Christiane Wirbelauer

Edward J Oakeley

Dimos Gaidatzis

Vijay K Tiwari

Dirk Schubeler

Affiliations

Soon will be listed here.

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.

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