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Ng, H.H. et al. MBD2 is a transcriptional repressor belonging to the MeCP1 histone deacetylase complex. Nat. Genet. 23, 58-61

Institute of Cell and Molecular Biology, University of Edinburgh, The King's Buildings, Edinburgh EH9 3JR, UK.
Nature Genetics (Impact Factor: 29.35). 10/1999; 23(1):58-61. DOI: 10.1038/12659
Source: PubMed

ABSTRACT

Mammalian DNA is methylated at many CpG dinucleotides. The biological consequences of methylation are mediated by a family of methyl-CpG binding proteins. The best characterized family member is MeCP2, a transcriptional repressor that recruits histone deacetylases. Our report concerns MBD2, which can bind methylated DNA in vivo and in vitro and has been reported to actively demethylate DNA (ref. 8). As DNA methylation causes gene silencing, the MBD2 demethylase is a candidate transcriptional activator. Using specific antibodies, however, we find here that MBD2 in HeLa cells is associated with histone deacetylase (HDAC) in the MeCP1 repressor complex. An affinity-purified HDAC1 corepressor complex also contains MBD2, suggesting that MeCP1 corresponds to a fraction of this complex. Exogenous MBD2 represses transcription in a transient assay, and repression can be relieved by the deacetylase inhibitor trichostatin A (TSA; ref. 12). In our hands, MBD2 does not demethylate DNA. Our data suggest that HeLa cells, which lack the known methylation-dependent repressor MeCP2, use an alternative pathway involving MBD2 to silence methylated genes.

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Available from: Hediye Erdjument-Bromage, May 01, 2015
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    • "The inhibitory effect of CpG island methylation on gene expression is mediated by the involvement of proteins with high affinity for methylated CpGs. These methyl CpG-binding proteins (MeCP1, MeCP2, MBDs and Kaiso)161718192021exert theirin the amino terminal tails of nucleosomal histones, including deacetylation (HDACs), methylation (HMTs) and acetylation (histone acetyltransferases (HAT). Specific molecular modifications on CpGs and nucleosomal histones affect the higher order of chromatin architecture and function by changing the interaction of histones with DNA or the contact between different histones in adjacent nucleosomes. "
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