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

TitleClosely related proteins MBD2 and MBD3 play distinctive but interacting roles in mouse development.
Publication TypeJournal Article
Year of Publication2001
AuthorsHendrich B, Guy J, Ramsahoye B, Wilson V, Bird A
JournalGenes Dev
Volume15
Issue6
Pagination710-23
Date Published2001 Mar 15
ISSN0890-9369
KeywordsAge Factors, Animals, Blotting, Northern, Blotting, Southern, Blotting, Western, Brain, Cell Line, Cell Nucleus, CpG Islands, DNA Methylation, DNA-Binding Proteins, Embryo, Mammalian, Expressed Sequence Tags, Gene Deletion, Gene Expression Regulation, Developmental, Genomic Imprinting, Genotype, Liver, Mice, Mice, Inbred C57BL, Mice, Mutant Strains, Models, Biological, Models, Genetic, Plasmids, Promoter Regions, Genetic, Protein Binding, Protein Structure, Tertiary, Spleen, Stem Cells, Transcription Factors, Transcription, Genetic, Transfection
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.

DOI10.1101/gad.194101
Alternate JournalGenes Dev.
PubMed ID11274056
PubMed Central IDPMC312657