Menafra Roberta, Brinkman Arie B, Matarese Filomena, Franci Gianluigi, Bartels Stefanie J J, Nguyen Luan, Shimbo Takashi, Wade Paul A, Hubner Nina C, Stunnenberg Hendrik G
Department of Molecular Biology, Nijmegen Centre for Molecular Life Sciences, Radboud University Nijmegen, Nijmegen, The Netherlands.
Laboratory of Molecular Carcinogenesis, National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina, United States of America.
PLoS One. 2014 Jun 13;9(6):e99603. doi: 10.1371/journal.pone.0099603. eCollection 2014.
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.
MBD2是核小体重塑去乙酰化酶（NuRD）复合物的一个亚基，据推测它通过将该复合物募集到甲基化DNA上来介导基因抑制。在本研究中，我们采用了一种MBD2标记方法来研究其全基因组结合特征。我们发现，在体内MBD2主要被募集到高度甲基化的CpG岛启动子上。有趣的是，MBD2结合在约400个CpG岛启动子子集转录起始位点下游约1 kb处，这些启动子的特征是存在活性组蛋白标记、RNA聚合酶II（Pol2）以及低至中等水平的基因表达和H3K36me3沉积。MCF-7细胞中这些标记的MBD2结合位点在一组原发性乳腺癌中甲基化增加，但在正常乳腺样本中未增加，这表明MBD2在乳腺癌中可能发挥作用。
