Mi2, an auto-antigen for dermatomyositis, is an ATP-dependent nucleosome remodeling factor

Nucleic Acids Res. 2001 Jun 15;29(12):2517-21. doi: 10.1093/nar/29.12.2517.

Abstract

Dynamic changes in chromatin structure play an important role in transcription regulation. Recent studies have revealed two mechanisms that alter chromatin structure. One involves ATP-dependent chromatin remodeling, and the other involves acetylation of the core histone tails. We have previously purified and characterized a multi-subunit protein complex, NuRD, which possesses both nucleosome remodeling and histone deacetylase activities. Despite extensive biochemical characterization of the complex, little is known about the functions of its individual components. In this study, we focused on Mi2, a component of the NuRD complex. We found that, similar to the native NuRD complex, recombinant Mi2 is a DNA-dependent, nucleosome-stimulated ATPase. Kinetic analysis of the ATP hydrolysis reaction indicated that the differential stimulation of the Mi2 ATPase by DNA and nucleosomes were primarily due to their differential effects on the turnover number of the reaction. Furthermore, we demonstrated that recombinant Mi2 is an efficient nucleosome remodeling factor when compared to that of the native NuRD complex. Our results define the biochemical function of Mi2 and set the stage for understanding the mechanism of nucleosome remodeling in a defined reconstituted system.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adenosine Triphosphatases / genetics
  • Adenosine Triphosphatases / immunology
  • Adenosine Triphosphatases / isolation & purification
  • Adenosine Triphosphatases / metabolism*
  • Adenosine Triphosphate / metabolism*
  • Autoantigens / genetics
  • Autoantigens / immunology
  • Autoantigens / isolation & purification
  • Autoantigens / metabolism*
  • DNA / chemistry
  • DNA / genetics
  • DNA / metabolism
  • DNA Helicases*
  • Dermatomyositis / immunology*
  • Enzyme Activation
  • Histone Deacetylases / chemistry*
  • Histone Deacetylases / genetics
  • Histone Deacetylases / metabolism
  • Histones / metabolism
  • Humans
  • Hydrolysis
  • Kinetics
  • Mi-2 Nucleosome Remodeling and Deacetylase Complex
  • Molecular Conformation
  • Nucleosomes / chemistry*
  • Nucleosomes / genetics
  • Nucleosomes / metabolism*
  • Recombinant Proteins / isolation & purification
  • Recombinant Proteins / metabolism
  • Sin3 Histone Deacetylase and Corepressor Complex

Substances

  • Autoantigens
  • CHD4 protein, human
  • Histones
  • Nucleosomes
  • Recombinant Proteins
  • Adenosine Triphosphate
  • DNA
  • Histone Deacetylases
  • Mi-2 Nucleosome Remodeling and Deacetylase Complex
  • Sin3 Histone Deacetylase and Corepressor Complex
  • Adenosine Triphosphatases
  • DNA Helicases