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DNA methylation directs genomic localization of Mbd2 and Mbd3 in embryonic stem cells

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...

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Autores principales: Hainer, Sarah J, McCannell, Kurtis N, Yu, Jun, Ee, Ly-Sha, Zhu, Lihua J, Rando, Oliver J, Fazzio, Thomas G
Formato: Online Artículo Texto
Lenguaje:English
Publicado: eLife Sciences Publications, Ltd 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5111885/
https://www.ncbi.nlm.nih.gov/pubmed/27849519
http://dx.doi.org/10.7554/eLife.21964
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author Hainer, Sarah J
McCannell, Kurtis N
Yu, Jun
Ee, Ly-Sha
Zhu, Lihua J
Rando, Oliver J
Fazzio, Thomas G
author_facet Hainer, Sarah J
McCannell, Kurtis N
Yu, Jun
Ee, Ly-Sha
Zhu, Lihua J
Rando, Oliver J
Fazzio, Thomas G
author_sort Hainer, Sarah J
collection PubMed
description 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. DOI: http://dx.doi.org/10.7554/eLife.21964.001
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spelling pubmed-51118852016-11-17 DNA methylation directs genomic localization of Mbd2 and Mbd3 in embryonic stem cells Hainer, Sarah J McCannell, Kurtis N Yu, Jun Ee, Ly-Sha Zhu, Lihua J Rando, Oliver J Fazzio, Thomas G eLife Developmental Biology and Stem Cells 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. DOI: http://dx.doi.org/10.7554/eLife.21964.001 eLife Sciences Publications, Ltd 2016-11-16 /pmc/articles/PMC5111885/ /pubmed/27849519 http://dx.doi.org/10.7554/eLife.21964 Text en © 2016, Hainer et al http://creativecommons.org/licenses/by/4.0/ This article is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use and redistribution provided that the original author and source are credited.
spellingShingle Developmental Biology and Stem Cells
Hainer, Sarah J
McCannell, Kurtis N
Yu, Jun
Ee, Ly-Sha
Zhu, Lihua J
Rando, Oliver J
Fazzio, Thomas G
DNA methylation directs genomic localization of Mbd2 and Mbd3 in embryonic stem cells
title DNA methylation directs genomic localization of Mbd2 and Mbd3 in embryonic stem cells
title_full DNA methylation directs genomic localization of Mbd2 and Mbd3 in embryonic stem cells
title_fullStr DNA methylation directs genomic localization of Mbd2 and Mbd3 in embryonic stem cells
title_full_unstemmed DNA methylation directs genomic localization of Mbd2 and Mbd3 in embryonic stem cells
title_short DNA methylation directs genomic localization of Mbd2 and Mbd3 in embryonic stem cells
title_sort dna methylation directs genomic localization of mbd2 and mbd3 in embryonic stem cells
topic Developmental Biology and Stem Cells
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5111885/
https://www.ncbi.nlm.nih.gov/pubmed/27849519
http://dx.doi.org/10.7554/eLife.21964
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