PARP-1 regulates chromatin structure and transcription through a KDM5B-dependent pathway

Mol Cell. 2010 Sep 10;39(5):736-49. doi: 10.1016/j.molcel.2010.08.014.


PARP-1 is an abundant nuclear enzyme that regulates gene expression, although the underlying mechanisms are unclear. We examined the interplay between PARP-1, histone 3 lysine 4 trimethylation (H3K4me3), and linker histone H1 in the chromatin-dependent control of transcription. We show that PARP-1 is required for a series of molecular outcomes at the promoters of PARP-1-regulated genes, leading to a permissive chromatin environment that allows loading of the RNA Pol II machinery. PARP-1 does so by (1) preventing demethylation of H3K4me3 through the PARylation, inhibition, and exclusion of the histone demethylase KDM5B; and (2) promoting the exclusion of H1 and the opening of promoter chromatin. Upon depletion of PARP-1, these outcomes do not occur efficiently. Interestingly, cellular signaling pathways can use the regulated depletion of PARP-1 to modulate these chromatin-related molecular outcomes. Collectively, our results help to elucidate the roles of PARP-1 in the regulation of chromatin structure and transcription.

Publication types

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

MeSH terms

  • Cell Line, Tumor
  • Chromatin / enzymology*
  • Chromatin / genetics
  • Gene Expression Regulation / physiology*
  • Histones / genetics
  • Histones / metabolism
  • Humans
  • Jumonji Domain-Containing Histone Demethylases
  • Nuclear Proteins / genetics
  • Nuclear Proteins / metabolism*
  • Poly (ADP-Ribose) Polymerase-1
  • Poly(ADP-ribose) Polymerases / genetics
  • Poly(ADP-ribose) Polymerases / metabolism*
  • Promoter Regions, Genetic / physiology*
  • RNA Polymerase II / genetics
  • RNA Polymerase II / metabolism
  • Repressor Proteins / genetics
  • Repressor Proteins / metabolism*
  • Signal Transduction / physiology
  • Transcription, Genetic / physiology*


  • Chromatin
  • Histones
  • Nuclear Proteins
  • Repressor Proteins
  • Jumonji Domain-Containing Histone Demethylases
  • KDM5B protein, human
  • PARP1 protein, human
  • Poly (ADP-Ribose) Polymerase-1
  • Poly(ADP-ribose) Polymerases
  • RNA Polymerase II