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 deacet ylation represent mechanisms to alter nucleosome structure. NuRD is a multi subunit complex containing nucleosome remodeling and histone deacetylase ac tivities. 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 cor e complex is severely compromised. A novel polypeptide highly related to th e metastasis-associated protein 1, MTA2, and the methyl-CpG-binding domain- containing protein, MBD3, were found to be subunits of the NuRD complex. MT A2 modulates the enzymatic activity of the histone deacetylase core complex . MBD3 mediates the association of MTA2 with the core histone deacetylase c omplex. 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 dir ects the complex to methylated DNA. NuRD may provide a means of gene silenc ing by DNA methylation.