Analysis of the NuRD subunits reveals a histone deacetylase core complex and a connection with DNA methylation

  1. Yi Zhang,
  2. Huck-Hui Ng,
  3. Hediye Erdjument-Bromage,
  4. Paul Tempst,
  5. Adrian Bird, and
  6. Danny Reinberg
  1. Howard Hughes Medical Institute (HHMI), 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; Institute of Cell and Molecular Biology, University of Edinburgh, Edinburgh EH9 3JR, UK; Molecular Biology Program, Memorial Sloan Kettering Cancer Center, New York, New York 10021 USA

Abstract

ATP-dependent nucleosome remodeling and core histone acetylation and deacetylation represent mechanisms to alter nucleosome structure. NuRD is a multisubunit complex containing nucleosome remodeling and histone deacetylase activities. The histone deacetylases HDAC1 and HDAC2 and the histone binding proteins RbAp48 and RbAp46 form a core complex shared between NuRD and Sin3-histone deacetylase complexes. The histone deacetylase activity of the core complex is severely compromised. A novel polypeptide highly related to themetastasis-associated protein 1, MTA2, and the methyl-CpG-bindingdomain-containing protein, MBD3, were found to be subunits of the NuRD complex. MTA2 modulates the enzymatic activity of the histone deacetylase core complex. MBD3 mediates the association of MTA2 with the core histone deacetylase complex. MBD3 does not directly bind methylated DNA but is highly related to MBD2, a polypeptide that binds to methylated DNA and has been reported to possess demethylase activity. MBD2 interacts with the NuRD complex and directs the complex to methylated DNA. NuRD may provide a means of gene silencing by DNA methylation.

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Footnotes

  • Present address: Lineberger Comprehensive Cancer Center, Deptartment of Biochemistry and Biophysics, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599-7295 USA.

  • Corresponding author.

  • E-MAIL reinbedf{at}umdnj.edu; FAX (732) 235-5294.

    • Received May 26, 1999.
    • Accepted June 23, 1999.
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