MBD2 is a transcriptional repressor belonging to the MeCP1 histone deacetylase complex

Abstract

Mammalian DNA is methylated at many CpG dinucleotides. The biological consequences of methylation are mediated by a family of methyl-CpG binding proteins^1,2,3,4. The best characterized family member is MeCP2, a transcriptional repressor that recruits histone deacetylases^5,6,7. Our report concerns MBD2, which can bind methylated DNA in vivo and in vitro ⁴ 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^1,9. An affinity-purified HDAC1 corepressor complex^10,11 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.