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Genome-wide analyses reveal a role of Polycomb in promoting hypomethylation of DNA methylation valleys

Overview of attention for article published in Genome Biology (Online Edition), February 2018
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Title
Genome-wide analyses reveal a role of Polycomb in promoting hypomethylation of DNA methylation valleys
Published in
Genome Biology (Online Edition), February 2018
DOI 10.1186/s13059-018-1390-8
Pubmed ID
Authors

Yuanyuan Li, Hui Zheng, Qiujun Wang, Chen Zhou, Lei Wei, Xuehui Liu, Wenhao Zhang, Yu Zhang, Zhenhai Du, Xiaowo Wang, Wei Xie

Abstract

Previous studies showed that the majority of developmental genes are devoid of DNA methylation at promoters even when they are repressed. Such hypomethylated regions at developmental genes are unusually large and extend well beyond proximal promoters, forming DNA methylation valleys (DMVs) or DNA methylation canyons. However, it remains elusive how most developmental genes can evade DNA methylation regardless of their transcriptional states. We show that DMVs are hypomethylated in development and are highly conserved across vertebrates. Importantly, DMVs are hotspots of regulatory regions for key developmental genes and show low levels of deamination mutation rates. By analyzing a panel of DNA methylomes from mouse tissues, we identify a subset of DMVs that are dynamically methylated. These DMVs are strongly enriched for Polycomb-deposited H3K27me3 when the associated genes are silenced, and surprisingly show elevated DNA methylation upon gene activation. 4C-seq analyses indicates that Polycomb-bound DMVs form insulated and self-interacting chromatin domains. Further investigations show that DNA hypomethylation is better correlated with the binding of Polycomb than with H3K27me3. In support of a role of Polycomb in DMV hypomethylation, we observe aberrant methylation in DMVs in mouse embryonic stem cells deficient in the EED protein. Finally, we show that Polycomb regulates hypomethylation of DMVs likely through ten-eleven translocation (TET) proteins. We show that Polycomb promotes the hypomethylation of DMVs near key developmental genes. These data reveal a delicate interplay between histone modifiers and DNA methylation, which contributes to their division at distinct gene targets, allowing lineage-specifying genes to largely maintain DNA methylation-free at regulatory elements.

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Mendeley readers

The data shown below were compiled from readership statistics for 143 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
Unknown 143 100%

Demographic breakdown

Readers by professional status Count As %
Student > Ph. D. Student 38 27%
Researcher 31 22%
Student > Bachelor 17 12%
Student > Master 16 11%
Professor 4 3%
Other 11 8%
Unknown 26 18%
Readers by discipline Count As %
Biochemistry, Genetics and Molecular Biology 75 52%
Agricultural and Biological Sciences 25 17%
Chemical Engineering 4 3%
Unspecified 3 2%
Nursing and Health Professions 2 1%
Other 8 6%
Unknown 26 18%

Attention Score in Context

This research output has an Altmetric Attention Score of 1. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 19 February 2020.
All research outputs
#13,045,581
of 17,020,562 outputs
Outputs from Genome Biology (Online Edition)
#3,367
of 3,550 outputs
Outputs of similar age
#252,041
of 373,537 outputs
Outputs of similar age from Genome Biology (Online Edition)
#1
of 1 outputs
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