Insight into the architecture of the NuRD complex: structure of the RbAp48-MTA1 subcomplex

J Biol Chem. 2014 Aug 8;289(32):21844-55. doi: 10.1074/jbc.M114.558940. Epub 2014 Jun 11.

Abstract

The nucleosome remodeling and deacetylase (NuRD) complex is a widely conserved transcriptional co-regulator that harbors both nucleosome remodeling and histone deacetylase activities. It plays a critical role in the early stages of ES cell differentiation and the reprogramming of somatic to induced pluripotent stem cells. Abnormalities in several NuRD proteins are associated with cancer and aging. We have investigated the architecture of NuRD by determining the structure of a subcomplex comprising RbAp48 and MTA1. Surprisingly, RbAp48 recognizes MTA1 using the same site that it uses to bind histone H4, showing that assembly into NuRD modulates RbAp46/48 interactions with histones. Taken together with other results, our data show that the MTA proteins act as scaffolds for NuRD complex assembly. We further show that the RbAp48-MTA1 interaction is essential for the in vivo integration of RbAp46/48 into the NuRD complex.

Keywords: Chromatin; Chromatin Structure; Gene Regulation; MTA1; NuRD Complex; Protein Assembly; Protein Structure; RBBP4; RbAp48.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Chromatin Assembly and Disassembly
  • Conserved Sequence
  • Crystallography, X-Ray
  • Histone Deacetylases / chemistry*
  • Histone Deacetylases / genetics
  • Histone Deacetylases / metabolism
  • Histones / metabolism
  • Humans
  • Mi-2 Nucleosome Remodeling and Deacetylase Complex / chemistry*
  • Mi-2 Nucleosome Remodeling and Deacetylase Complex / genetics
  • Mi-2 Nucleosome Remodeling and Deacetylase Complex / metabolism
  • Models, Molecular
  • Molecular Sequence Data
  • Nuclear Proteins / chemistry
  • Nuclear Proteins / genetics
  • Nuclear Proteins / metabolism
  • Nucleosomes / metabolism
  • Protein Interaction Domains and Motifs
  • Repressor Proteins / chemistry*
  • Repressor Proteins / genetics
  • Repressor Proteins / metabolism
  • Retinoblastoma-Binding Protein 4 / chemistry*
  • Retinoblastoma-Binding Protein 4 / genetics
  • Retinoblastoma-Binding Protein 4 / metabolism
  • Retinoblastoma-Binding Protein 7 / chemistry
  • Retinoblastoma-Binding Protein 7 / genetics
  • Retinoblastoma-Binding Protein 7 / metabolism
  • Sequence Homology, Amino Acid
  • Trans-Activators
  • Transcription Factors / chemistry
  • Transcription Factors / genetics
  • Transcription Factors / metabolism

Substances

  • Histones
  • MTA1 protein, human
  • Nuclear Proteins
  • Nucleosomes
  • RBBP4 protein, human
  • RBBP7 protein, human
  • Repressor Proteins
  • Retinoblastoma-Binding Protein 4
  • Retinoblastoma-Binding Protein 7
  • Trans-Activators
  • Transcription Factors
  • ZFPM1 protein, human
  • Histone Deacetylases
  • Mi-2 Nucleosome Remodeling and Deacetylase Complex

Associated data

  • PDB/4PBY
  • PDB/4PBZ
  • PDB/4PC0