The N-terminal Region of Chromodomain Helicase DNA-binding Protein 4 (CHD4) Is Essential for Activity and Contains a High Mobility Group (HMG) Box-like-domain That Can Bind Poly(ADP-ribose)

J Biol Chem. 2016 Jan 8;291(2):924-38. doi: 10.1074/jbc.M115.683227. Epub 2015 Nov 12.

Abstract

Chromodomain Helicase DNA-binding protein 4 (CHD4) is a chromatin-remodeling enzyme that has been reported to regulate DNA-damage responses through its N-terminal region in a poly(ADP-ribose) polymerase-dependent manner. We have identified and determined the structure of a stable domain (CHD4-N) in this N-terminal region. The-fold consists of a four-α-helix bundle with structural similarity to the high mobility group box, a domain that is well known as a DNA binding module. We show that the CHD4-N domain binds with higher affinity to poly(ADP-ribose) than to DNA. We also show that the N-terminal region of CHD4, although not CHD4-N alone, is essential for full nucleosome remodeling activity and is important for localizing CHD4 to sites of DNA damage. Overall, these data build on our understanding of how CHD4-NuRD acts to regulate gene expression and participates in the DNA-damage response.

Keywords: CHD4; DNA binding protein; DNA damage; HMG-box; chromatin remodeling; nucleosome; nucleosome remodeling deacetylase (NuRD); poly(ADP-ribose).

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Autoantigens / chemistry*
  • Autoantigens / metabolism*
  • Chromatin Assembly and Disassembly
  • Conserved Sequence
  • DNA / metabolism
  • DNA Breaks, Double-Stranded
  • DNA Damage
  • HEK293 Cells
  • HMG-Box Domains*
  • Humans
  • Mi-2 Nucleosome Remodeling and Deacetylase Complex / chemistry*
  • Mi-2 Nucleosome Remodeling and Deacetylase Complex / metabolism*
  • Models, Molecular
  • Molecular Sequence Data
  • Nucleosomes / metabolism
  • Peptides / metabolism
  • Poly Adenosine Diphosphate Ribose / metabolism*
  • Protein Binding
  • Protein Structure, Secondary
  • Sequence Deletion
  • Structure-Activity Relationship

Substances

  • Autoantigens
  • CHD4 protein, human
  • Nucleosomes
  • Peptides
  • Poly Adenosine Diphosphate Ribose
  • DNA
  • Mi-2 Nucleosome Remodeling and Deacetylase Complex

Associated data

  • PDB/1j5n
  • PDB/1kx5
  • PDB/2crj
  • PDB/2n5n
  • PDB/3nm9