NAD+-dependent modulation of chromatin structure and transcription by nucleosome binding properties of PARP-1

Cell. 2004 Dec 17;119(6):803-14. doi: 10.1016/j.cell.2004.11.002.


PARP-1 is the most abundantly expressed member of a family of proteins that catalyze the transfer of ADP-ribose units from NAD+ to target proteins. Herein, we describe previously uncharacterized nucleosome binding properties of PARP-1 that promote the formation of compact, transcriptionally repressed chromatin structures. PARP-1 binds in a specific manner to nucleosomes and modulates chromatin structure through NAD+-dependent automodification, without modifying core histones or promoting the disassembly of nucleosomes. The automodification activity of PARP-1 is potently stimulated by nucleosomes, causing the release of PARP-1 from chromatin. The NAD+-dependent activities of PARP-1 are reversed by PARG, a poly(ADP-ribose) glycohydrolase, and are inhibited by ATP. In vivo, PARP-1 incorporation is associated with transcriptionally repressed chromatin domains that are spatially distinct from both histone H1-repressed domains and actively transcribed regions. Thus, PARP-1 functions both as a structural component of chromatin and a modulator of chromatin structure through its intrinsic enzymatic activity.

Publication types

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

MeSH terms

  • Adenosine Triphosphate / metabolism
  • Cell Nucleus / metabolism
  • Chromatin / metabolism*
  • Glycoside Hydrolases / metabolism
  • Histones / metabolism*
  • Humans
  • Macromolecular Substances / metabolism
  • NAD / metabolism*
  • Nucleosomes / metabolism*
  • Poly(ADP-ribose) Polymerases / metabolism*
  • Recombinant Proteins / metabolism


  • Chromatin
  • Histones
  • Macromolecular Substances
  • Nucleosomes
  • Recombinant Proteins
  • NAD
  • Adenosine Triphosphate
  • Poly(ADP-ribose) Polymerases
  • Glycoside Hydrolases
  • poly ADP-ribose glycohydrolase