Genome-wide binding of MBD2 reveals strong preference for highly methylated loci

Roberta Menafra; Arie B. Brinkman; Filomena Matarese; Gianluigi Franci; Stefanie J.J. Bartels; Luan Nguyen; Takashi Shimbo; Paul A. Wade; Nina C. Hubner; Hendrik G. Stunnenberg

doi:10.1371/journal.pone.0099603

Genome-wide binding of MBD2 reveals strong preference for highly methylated loci

Roberta Menafra, Arie B. Brinkman, Filomena Matarese, Gianluigi Franci, Stefanie J.J. Bartels, Luan Nguyen, Takashi Shimbo, Paul A. Wade, Nina C. Hubner, Hendrik G. Stunnenberg

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40 Citations (Scopus)

Abstract

MBD2 is a subunit of the NuRD complex that is postulated to mediate gene repression via recruitment of the complex to methylated DNA. In this study we adopted an MBD2 tagging-approach to study its genome wide binding characteristics. We show that in vivo MBD2 is mainly recruited to CpG island promoters that are highly methylated. Interestingly, MBD2 binds around 1 kb downstream of the transcription start site of a subset of ∼400 CpG island promoters that are characterized by the presence of active histone marks, RNA polymerase II (Pol2) and low to medium gene expression levels and H3K36me3 deposition. These tagged-MBD2 binding sites in MCF-7 show increased methylation in a cohort of primary breast cancers but not in normal breast samples, suggesting a putative role for MBD2 in breast cancer.

Original language	English
Article number	e99603
Journal	PLoS ONE
Volume	9
Issue number	6
DOIs	https://doi.org/10.1371/journal.pone.0099603
Publication status	Published - 13 Jun 2014
Externally published	Yes

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title = "Genome-wide binding of MBD2 reveals strong preference for highly methylated loci",

abstract = "MBD2 is a subunit of the NuRD complex that is postulated to mediate gene repression via recruitment of the complex to methylated DNA. In this study we adopted an MBD2 tagging-approach to study its genome wide binding characteristics. We show that in vivo MBD2 is mainly recruited to CpG island promoters that are highly methylated. Interestingly, MBD2 binds around 1 kb downstream of the transcription start site of a subset of ∼400 CpG island promoters that are characterized by the presence of active histone marks, RNA polymerase II (Pol2) and low to medium gene expression levels and H3K36me3 deposition. These tagged-MBD2 binding sites in MCF-7 show increased methylation in a cohort of primary breast cancers but not in normal breast samples, suggesting a putative role for MBD2 in breast cancer.",

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AU - Menafra, Roberta

AU - Brinkman, Arie B.

AU - Matarese, Filomena

AU - Franci, Gianluigi

AU - Bartels, Stefanie J.J.

AU - Nguyen, Luan

AU - Shimbo, Takashi

AU - Wade, Paul A.

AU - Hubner, Nina C.

AU - Stunnenberg, Hendrik G.

PY - 2014/6/13

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AB - MBD2 is a subunit of the NuRD complex that is postulated to mediate gene repression via recruitment of the complex to methylated DNA. In this study we adopted an MBD2 tagging-approach to study its genome wide binding characteristics. We show that in vivo MBD2 is mainly recruited to CpG island promoters that are highly methylated. Interestingly, MBD2 binds around 1 kb downstream of the transcription start site of a subset of ∼400 CpG island promoters that are characterized by the presence of active histone marks, RNA polymerase II (Pol2) and low to medium gene expression levels and H3K36me3 deposition. These tagged-MBD2 binding sites in MCF-7 show increased methylation in a cohort of primary breast cancers but not in normal breast samples, suggesting a putative role for MBD2 in breast cancer.

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Genome-wide binding of MBD2 reveals strong preference for highly methylated loci

Abstract

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