Nature Genetics
23, 58 - 61 (1999)
doi:10.1038/12659
MBD2 is a transcriptional repressor belonging to the MeCP1 histone deacetylase
complexHuck-Hui Ng1, Yi Zhang2, Brian Hendrich1, Colin A. Johnson3, Bryan M. Turner3, Hediye Erdjument-Bromage4, Paul Tempst4, Danny Reinberg2
& Adrian Bird11
Institute of Cell and Molecular Biology, University of Edinburgh, The King's Buildings, Edinburgh EH9 3JR, UK. 2
Howard Hughes Medical Institute, Division of Nucleic Acids Enzymology, Department of Biochemistry, University of Medicine and Dentistry of New Jersey, Robert Wood Johnson Medical School, Piscataway, New Jersey 08854, USA. 3
Department of Anatomy, The Medical School, University of Birmingham, Birmingham B15 2TT, UK. 4
Molecular Biology Program, Memorial Sloan Kettering Cancer Center, 1275 York Avenue, New York, New York 10021, USA.
Correspondence should be addressed to Adrian Bird A.Bird@ed.ac.ukMammalian DNA is methylated at many CpG dinucleotides. The biological consequences
of methylation are mediated by a family of methyl-CpG binding proteins1,
2,
3,
4. The best characterized family member is MeCP2, a transcriptional
repressor that recruits histone deacetylases5,
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 complex1,
9.
An affinity-purified HDAC1 corepressor complex10,
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.
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