DNA methylation directs genomic localization of Mbd2 and Mbd3 in embryonic stem cells
Authors
Hainer, Sarah J.McCannell, Kurtis N.
Yu, Jun
Ee, Ly-Sha
Zhu, Lihua (Julie)
Rando, Oliver J.
Fazzio, Thomas G.
UMass Chan Affiliations
UMass Metabolic NetworkDepartment of Biochemistry and Molecular Pharmacology
Department of Molecular, Cell, and Cancer Biology
Document Type
Journal ArticlePublication Date
2016-11-16Keywords
DNA hydroxymethylationDNA methylation
NuRD
chromatin
chromosomes
developmental biology
embryonic stem cells
genes
mouse
nucleosome
stem cells
Cell Biology
Developmental Biology
Molecular Biology
Metadata
Show full item recordAbstract
Cytosine methylation is an epigenetic and regulatory mark that functions in part through recruitment of chromatin remodeling complexes containing methyl-CpG binding domain (MBD) proteins. Two MBD proteins, Mbd2 and Mbd3, were previously shown to bind methylated or hydroxymethylated DNA, respectively; however, both of these findings have been disputed. Here, we investigated this controversy using experimental approaches and re-analysis of published data and find no evidence for methylation-independent functions of Mbd2 or Mbd3. We show that chromatin localization of Mbd2 and Mbd3 is highly overlapping and, unexpectedly, we find Mbd2 and Mbd3 are interdependent for chromatin association. Further investigation reveals that both proteins are required for normal levels of cytosine methylation and hydroxymethylation in murine embryonic stem cells. Furthermore, Mbd2 and Mbd3 regulate overlapping sets of genes that are also regulated by DNA methylation/hydroxymethylation factors. These findings reveal an interdependent regulatory mechanism mediated by the DNA methylation machinery and its readers.Source
Elife. 2016 Nov 16;5. pii: e21964. doi: 10.7554/eLife.21964. Link to article on publisher's siteDOI
10.7554/eLife.21964Permanent Link to this Item
http://hdl.handle.net/20.500.14038/40190PubMed ID
27849519Related Resources
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© 2016, Hainer et al. Elife. 2016 Nov 16;5. pii: e21964. doi: 10.7554/eLife.21964. Link to article on publisher's siteDistribution License
http://creativecommons.org/licenses/by/4.0/ae974a485f413a2113503eed53cd6c53
10.7554/eLife.21964
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Except where otherwise noted, this item's license is described as © 2016, Hainer et al. Elife. 2016 Nov 16;5. pii: e21964. doi: 10.7554/eLife.21964. <a href="https://doi.org/10.7554/eLife.21964">Link to article on publisher's site</a>