PMID- 10471499
OWN - NLM
STAT- MEDLINE
DCOM- 19990923
LR  - 20121115
IS  - 1061-4036 (Print)
IS  - 1061-4036 (Linking)
VI  - 23
IP  - 1
DP  - 1999 Sep
TI  - MBD2 is a transcriptional repressor belonging to the MeCP1 histone deacetylase
      complex.
PG  - 58-61
AB  - 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.
FAU - Ng, H H
AU  - Ng HH
AD  - Institute of Cell and Molecular Biology, University of Edinburgh, The King's
      Buildings, Edinburgh EH9 3JR, UK.
FAU - Zhang, Y
AU  - Zhang Y
FAU - Hendrich, B
AU  - Hendrich B
FAU - Johnson, C A
AU  - Johnson CA
FAU - Turner, B M
AU  - Turner BM
FAU - Erdjument-Bromage, H
AU  - Erdjument-Bromage H
FAU - Tempst, P
AU  - Tempst P
FAU - Reinberg, D
AU  - Reinberg D
FAU - Bird, A
AU  - Bird A
LA  - eng
GR  - Wellcome Trust/United Kingdom
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - Nat Genet
JT  - Nature genetics
JID - 9216904
RN  - 0 (DNA-Binding Proteins)
RN  - 0 (Enzyme Inhibitors)
RN  - 0 (Hydroxamic Acids)
RN  - 0 (MBD2 protein)
RN  - 0 (MeCP1 histone deacetylase complex, human)
RN  - 0 (MeCP1 histone deacetylase complex, mouse)
RN  - 0 (MeCP1 histone deacetylase complex, rat)
RN  - 0 (Recombinant Proteins)
RN  - 0 (Repressor Proteins)
RN  - 0 (SIN3A transcription factor)
RN  - 3X2S926L3Z (trichostatin A)
RN  - EC 3.5.1.98 (Histone Deacetylases)
SB  - IM
CIN - Nat Genet. 1999 Sep;23(1):5-6. PMID: 10471484
MH  - Amino Acid Sequence
MH  - Animals
MH  - Base Sequence
MH  - Brain/metabolism
MH  - DNA Methylation
MH  - DNA-Binding Proteins/*physiology
MH  - Enzyme Inhibitors/pharmacology
MH  - HeLa Cells
MH  - Histone Deacetylases/*physiology
MH  - Humans
MH  - Hydroxamic Acids/pharmacology
MH  - Mice
MH  - Models, Genetic
MH  - Molecular Sequence Data
MH  - Rats
MH  - Recombinant Proteins/metabolism
MH  - Repressor Proteins/metabolism/*physiology
MH  - *Transcription, Genetic
MH  - Transcriptional Activation
MH  - Transfection
EDAT- 1999/09/02 09:00
MHDA- 2001/03/23 10:01
CRDT- 1999/09/02 09:00
PHST- 1999/09/02 09:00 [pubmed]
PHST- 2001/03/23 10:01 [medline]
PHST- 1999/09/02 09:00 [entrez]
AID - 10.1038/12659 [doi]
PST - ppublish
SO  - Nat Genet. 1999 Sep;23(1):58-61. doi: 10.1038/12659.