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PMID: 11274056 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

Closely related proteins MBD2 and MBD3 play distinctive but interacting roles in mouse development.

Genes & development ·Vol. 15 ·No. 6 ·2001-03-15 ·Pages 710-23

Hendrich B, Guy J, Ramsahoye B, Wilson VA, Bird A

Abstract

MBD2 and MBD3 are closely related proteins with consensus methyl-CpG binding domains. MBD2 is a transcriptional repressor that specifically binds to methylated DNA and is a component of the MeCP1 protein complex. In contrast, MBD3 fails to bind methylated DNA in murine cells, and is a component of the Mi-2/NuRD corepressor complex. We show by gene targeting that the two proteins are not functionally redundant in mice, as Mbd3-/- mice die during early embryogenesis, whereas Mbd2-/- mice are viable and fertile. Maternal behavior of Mbd2-/- mice is however defective and, at the molecular level, Mbd2-/- mice lack a component of MeCP1. Mbd2-mutant cells fail to fully silence transcription from exogenous methylated templates, but inappropriate activation of endogenous imprinted genes or retroviral sequences was not detected. Despite their differences, Mbd3 and Mbd2 interact genetically suggesting a functional relationship. Genetic and biochemical data together favor the view that MBD3 is a key component of the Mi-2/NuRD corepressor complex, whereas MBD2 may be one of several factors that can recruit this complex to DNA.

MeSH Terms
Age Factors Animals Blotting, Northern Blotting, Southern Blotting, Western Brain/metabolism Cell Line Cell Nucleus/metabolism CpG Islands DNA Methylation DNA-Binding Proteins/genetics,metabolism,physiology Embryo, Mammalian/metabolism Expressed Sequence Tags Gene Deletion Gene Expression Regulation, Developmental Genomic Imprinting Genotype Liver/metabolism Mice Mice, Inbred C57BL Mice, Mutant Strains Models, Biological Models, Genetic Plasmids/metabolism Promoter Regions, Genetic Protein Binding Protein Structure, Tertiary Spleen/metabolism Stem Cells/cytology Transcription Factors Transcription, Genetic Transfection
Chemicals
DNA-Binding Proteins MBD2 protein Mbd3 protein, mouse Transcription Factors
Authors & Affiliations
5 authors, click to expand affiliations / ORCID
Hendrich B
Wellcome Trust Centre for Cell Biology, Institute of Cell and Molecular Biology, The University of Edinburgh, Michael Swann Building, The King's Buildings, Edinburgh EH9 3JR, Scotland. Brian.Hendrich@ed.ac.uk
Guy J
Ramsahoye B
Wilson V A
Bird A
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Article Info
Journal
Genes & development
Abbr.
Genes Dev
ISSN
0890-9369
DOI
10.1101/gad.194101
Email
brian.hendrich@ed.ac.uk
Published
2001-03-15
Pages
710-23
Language
English
Region
United States
NLM ID
8711660
PMCID
PMC312657
Subset
IM
External Links
PubMed source DOI: 10.1101/gad.194101 PMC Full Text View journal details
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