Analysis of the NuRD subunits reveals a histone deacetylase core complex and a connection with DNA methylation.
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 the metastasis-associated protein 1, MTA2, and the methyl-CpG-binding domain-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.
Zhang
Y
Y
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.
Ng
H H
HH
Erdjument-Bromage
H
H
Tempst
P
P
Bird
A
A
Reinberg
D
D
D000251:Adenosine Triphosphatases; D000595:Amino Acid Sequence; D001324:Autoantigens / Q000302:isolation & purification / Q000378:metabolism; D001483:Base Sequence; D002352:Carrier Proteins / Q000737:chemistry / Q000235:genetics / Q000302:isolation & purification / Q000378:metabolism*; D003001:Cloning, Molecular; D004247:DNA / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D004265:DNA Helicases; D019175:DNA Methylation; D004268:DNA-Binding Proteins / Q000737:chemistry / Q000235:genetics / Q000302:isolation & purification / Q000378:metabolism*; D006367:HeLa Cells; D056284:Histone Deacetylase 1; D056464:Histone Deacetylase 2; D006655:Histone Deacetylases / Q000737:chemistry / Q000235:genetics / Q000302:isolation & purification / Q000378:metabolism*; D006801:Humans; D056245:Mi-2 Nucleosome Remodeling and Deacetylase Complex; D008969:Molecular Sequence Data; D009097:Multienzyme Complexes / Q000737:chemistry* / Q000235:genetics / Q000302:isolation & purification / Q000378:metabolism; D009687:Nuclear Proteins / Q000302:isolation & purification / Q000378:metabolism; D009707:Nucleosomes / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D011485:Protein Binding; D011993:Recombinant Fusion Proteins / Q000302:isolation & purification / Q000378:metabolism; D012097:Repressor Proteins; D056505:Retinoblastoma-Binding Protein 4; D056524:Retinoblastoma-Binding Protein 7; D017386:Sequence Homology, Amino Acid; D014157:Transcription Factors
D001324:Autoantigens; C115323:CHD4 protein, human; D002352:Carrier Proteins; D004268:DNA-Binding Proteins; C115368:MBD2 protein; C115369:MBD3 protein, human; C492013:Mbd3 protein, mouse; D009097:Multienzyme Complexes; D009687:Nuclear Proteins; D009707:Nucleosomes; C082637:RBBP4 protein, human; C490746:RBBP7 protein, human; C489969:Rbbp4 protein, mouse; D011993:Recombinant Fusion Proteins; D012097:Repressor Proteins; D056505:Retinoblastoma-Binding Protein 4; D056524:Retinoblastoma-Binding Protein 7; D014157:Transcription Factors; D004247:DNA; C120917:MTA2 protein, human; C110550:HDAC1 protein, human; C533424:Hdac2 protein, mouse; D056284:Histone Deacetylase 1; D056464:Histone Deacetylase 2; D006655:Histone Deacetylases; D056245:Mi-2 Nucleosome Remodeling and Deacetylase Complex; D000251:Adenosine Triphosphatases; D004265:DNA Helicases