MBD2 is a transcriptional repressor belonging to the MeCP1 histone deacetylase complex.
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.
Ng
H H
HH
Institute of Cell and Molecular Biology, University of Edinburgh, The King's Buildings, Edinburgh EH9 3JR, UK.
Zhang
Y
Y
Hendrich
B
B
Johnson
C A
CA
Turner
B M
BM
Erdjument-Bromage
H
H
Tempst
P
P
Reinberg
D
D
Bird
A
A
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D001921:Brain / Q000378:metabolism; D019175:DNA Methylation; D004268:DNA-Binding Proteins / Q000502:physiology*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006367:HeLa Cells; D006655:Histone Deacetylases / Q000502:physiology*; D006801:Humans; D006877:Hydroxamic Acids / Q000494:pharmacology; D051379:Mice; D008957:Models, Genetic; D008969:Molecular Sequence Data; D051381:Rats; D011994:Recombinant Proteins / Q000378:metabolism; D012097:Repressor Proteins / Q000378:metabolism / Q000502:physiology*; D056264:Sin3 Histone Deacetylase and Corepressor Complex; D014158:Transcription, Genetic; D015533:Transcriptional Activation; D014162:Transfection
D004268:DNA-Binding Proteins; D004791:Enzyme Inhibitors; D006877:Hydroxamic Acids; C115368:MBD2 protein; C489689:MeCP1 histone deacetylase complex, human; C489690:MeCP1 histone deacetylase complex, mouse; C077490:MeCP1 histone deacetylase complex, rat; D011994:Recombinant Proteins; D012097:Repressor Proteins; C099683:SIN3A transcription factor; C012589:trichostatin A; D006655:Histone Deacetylases; D056264:Sin3 Histone Deacetylase and Corepressor Complex