Abstract
Mammalian DNA is methylated at many CpG dinucleotides. The
biological consequences of methylation are mediated by a family
of methyl-CpG binding proteins (1–4). 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 vitro4 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 methylationdependent
repressor MeCP2, use an alternative pathway involving
MBD2 to silence methylated genes.
