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

Mammalian DNA is methylated at many CpG dinucleotides. The biological conse quences of methylation are mediated by a family of methyl-CpG binding prote ins(1-4). The best characterized family member is MeCP2, a transcriptional repressor that recruits histone deacetylases(5-7). Our report concerns MBD2 , which can bind methylated DNA in vivo and in vitro(4) and has been report ed to actively demethylate DNA (ref. 8). As DNA methylation causes gene sil encing, the MBD2 demethylase is a candidate transcriptional activator. Usin g specific antibodies, however, we find here that MBD2 in Hela cells is ass ociated 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 he r elieved by the deacetylase inhibitor trichostatin A (TSA; ref. 12). in our hands, MBDZ does not demethylate DNA. Our data suggest that Hela cells, whi ch lack the known methylation-dependent repressor MeCP2, use an alternative pathway involving MBD2 to silence methylated genes.