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PMID: 16428440 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

MBD2/NuRD and MBD3/NuRD, two distinct complexes with different biochemical and functional properties.

Molecular and cellular biology ·Vol. 26 ·No. 3 ·2006-02-00 ·Pages 843-51

Le Guezennec X, Vermeulen M, Brinkman AB, Hoeijmakers WA, Cohen A, Lasonder E, Stunnenberg HG

Abstract

The human genome contains a number of methyl CpG binding proteins that translate DNA methylation into a physiological response. To gain insight into the function of MBD2 and MBD3, we first applied protein tagging and mass spectrometry. We show that MBD2 and MBD3 assemble into mutually exclusive distinct Mi-2/NuRD-like complexes, called MBD2/NuRD and MBD3/NuRD. We identified DOC-1, a putative tumor suppressor, as a novel core subunit of MBD2/NuRD as well as MBD3/NuRD. PRMT5 and its cofactor MEP50 were identified as specific MBD2/NuRD interactors. PRMT5 stably and specifically associates with and methylates the RG-rich N terminus of MBD2. Chromatin immunoprecipitation experiments revealed that PRMT5 and MBD2 are recruited to CpG islands in a methylation-dependent manner in vivo and that H4R3, a substrate of PRMT, is methylated at these loci. Our data show that MBD2/NuRD and MBD3/NuRD are distinct protein complexes with different biochemical and functional properties.

MeSH Terms
Adaptor Proteins, Signal Transducing/metabolism Base Sequence Cells, Cultured Chromatin/metabolism Cytokines/metabolism DNA Methylation DNA-Binding Proteins/metabolism Histone Deacetylases/metabolism Humans Intracellular Signaling Peptides and Proteins Mi-2 Nucleosome Remodeling and Deacetylase Complex Molecular Sequence Data Protein Methyltransferases/metabolism Protein-Arginine N-Methyltransferases Tumor Suppressor Proteins
Chemicals
Adaptor Proteins, Signal Transducing Chromatin Cytokines DNA-Binding Proteins FILIP1L protein, human Intracellular Signaling Peptides and Proteins MBD2 protein, human MBD3 protein, human MEP50 protein, human Tumor Suppressor Proteins Protein Methyltransferases PRMT5 protein, human Protein-Arginine N-Methyltransferases Histone Deacetylases Mi-2 Nucleosome Remodeling and Deacetylase Complex
Authors & Affiliations
7 authors, click to expand affiliations / ORCID
Le Guezennec Xavier
Department of Molecular Biology, NCMLS M850/3.79, Radboud University, P.O. Box 9101, 6500 HB Nijmegen, The Netherlands.
Vermeulen Michiel
Brinkman Arie B
Hoeijmakers Wieteke A M
Cohen Adrian
Lasonder Edwin
Stunnenberg Hendrik G
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Article Info
Journal
Molecular and cellular biology
Abbr.
Mol Cell Biol
ISSN
0270-7306
DOI
10.1128/MCB.26.3.843-851.2006
Published
2006-02-00
Pages
843-51
Language
English
Region
United States
NLM ID
8109087
PMCID
PMC1347035
Subset
IM
External Links
PubMed source DOI: 10.1128/MCB.26.3.843-851.2006 PMC Full Text View journal details
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