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

Research output: Contribution to journal › Article › peer-review

44 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.",

author = "Roberta Menafra and Brinkman, \{Arie B.\} and Filomena Matarese and Gianluigi Franci and Bartels, \{Stefanie J.J.\} and Luan Nguyen and Takashi Shimbo and Wade, \{Paul A.\} and Hubner, \{Nina C.\} and Stunnenberg, \{Hendrik G.\}",

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doi = "10.1371/journal.pone.0099603",

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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

Y1 - 2014/6/13

N2 - 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.

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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DO - 10.1371/journal.pone.0099603

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JO - PloS one

JF - PloS one

IS - 6

M1 - e99603

ER -

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

Abstract

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