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PMID: 21964573 Published · epublish English Journal Article Research Support, N.I.H., Intramural Research Support, Non-U.S. Gov't

Identification of genetic elements that autonomously determine DNA methylation states.

Nature genetics ·Vol. 43 ·No. 11 ·2011-10-02 ·Pages 1091-7

Lienert F, Wirbelauer C, Som I, Dean A, Mohn F, Schübeler D

Abstract

Cytosine methylation is a repressive, epigenetically propagated DNA modification. Although patterns of DNA methylation seem tightly regulated in mammals, it is unclear how these are specified and to what extent this process entails genetic or epigenetic regulation. To dissect the role of the underlying DNA sequence, we sequentially inserted over 50 different DNA elements into the same genomic locus in mouse stem cells. Promoter sequences of approximately 1,000 bp autonomously recapitulated correct DNA methylation in pluripotent cells. Moreover, they supported proper de novo methylation during differentiation. Truncation analysis revealed that this regulatory potential is contained within small methylation-determining regions (MDRs). MDRs can mediate both hypomethylation and de novo methylation in cis, and their activity depends on developmental state, motifs for DNA-binding factors and a critical CpG density. These results demonstrate that proximal sequence elements are both necessary and sufficient for regulating DNA methylation and reveal basic constraints of this regulation.

MeSH Terms
Animals CpG Islands DNA Methylation Mutation Promoter Regions, Genetic Stem Cells/metabolism
Authors & Affiliations
6 authors, click to expand affiliations / ORCID
Lienert Florian
Friedrich Miescher Institute for Biomedical Research, Basel, Switzerland.
Wirbelauer Christiane
Som Indrani
Dean Ann
Mohn Fabio
Schübeler Dirk
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Article Info
Journal
Nature genetics
Abbr.
Nat Genet
ISSN
1546-1718
DOI
10.1038/ng.946
Published
2011-10-02
Epub
2011-00-02
Pages
1091-7
Language
English
Region
United States
NLM ID
9216904
Subset
IM
Grants
Intramural NIH HHS · United States
Corrections
CommentIn
PMID: 22030606
CommentIn
PMID: 22056134
External Links
PubMed source DOI: 10.1038/ng.946 View journal details
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