Histone H1 poly[ADP]-ribosylation regulates the chromatin alterations required for learning consolidation

J Neurosci. 2010 Oct 6;30(40):13305-13. doi: 10.1523/JNEUROSCI.3010-10.2010.

Abstract

Memory formation requires changes in gene expression, which are regulated by the activation of transcription factors and by changes in epigenetic factors. Poly[ADP]-ribosylation of nuclear proteins has been postulated as a chromatin modification involved in memory consolidation, although the mechanisms involved are not well characterized. Here we demonstrate that poly[ADP]-ribose polymerase 1 (PARP-1) activity and the poly[ADP]-ribosylation of proteins over a specific time course is required for the changes in synaptic plasticity related to memory stabilization in mice. At the molecular level, histone H1 poly[ADP]-ribosylation was evident in the hippocampus after the acquisition period, and it was selectively released in a PARP-1-dependent manner at the promoters of cAMP response element-binding protein and nuclear factor-κB dependent genes associated with learning and memory. These findings suggest that histone H1 poly[ADP]-ribosylation, and its loss at specific loci, is an epigenetic mechanism involved in the reprogramming of neuronal gene expression required for memory consolidation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Chromatin / genetics
  • Chromatin / metabolism*
  • Epigenesis, Genetic / genetics
  • Exploratory Behavior / physiology
  • Gene Expression Regulation / physiology
  • Genetic Loci / genetics
  • Hippocampus / cytology
  • Hippocampus / metabolism
  • Hippocampus / physiology
  • Histones / metabolism*
  • Histones / physiology
  • Learning / physiology*
  • Male
  • Memory / physiology
  • Mice
  • Neuronal Plasticity / genetics
  • Neuronal Plasticity / physiology
  • Poly (ADP-Ribose) Polymerase-1
  • Poly Adenosine Diphosphate Ribose / metabolism*
  • Poly Adenosine Diphosphate Ribose / physiology
  • Poly(ADP-ribose) Polymerases / metabolism
  • Poly(ADP-ribose) Polymerases / physiology
  • Promoter Regions, Genetic / genetics
  • Proteins / metabolism*
  • Proteins / physiology
  • Synaptic Transmission / genetics

Substances

  • Chromatin
  • Histones
  • Proteins
  • poly(ADP)-ribosylated proteins
  • Poly Adenosine Diphosphate Ribose
  • Parp1 protein, mouse
  • Poly (ADP-Ribose) Polymerase-1
  • Poly(ADP-ribose) Polymerases