Detection of histone acetylation levels in the dorsal hippocampus reveals early tagging on specific residues of H2B and H4 histones in response to learning

PLoS One. 2013;8(3):e57816. doi: 10.1371/journal.pone.0057816. Epub 2013 Mar 4.


The recent literature provides evidence that epigenetic mechanisms such as DNA methylation and histone modification are crucial to gene transcription linked to synaptic plasticity in the mammalian brain--notably in the hippocampus--and memory formation. We measured global histone acetylation levels in the rat hippocampus at an early stage of spatial or fear memory formation. We found that H3, H4 and H2B underwent differential acetylation at specific sites depending on whether rats had been exposed to the context of a task without having to learn or had to learn about a place or fear therein: H3K9K14 acetylation was mostly responsive to any experimental conditions compared to naive animals, whereas H2B N-terminus and H4K12 acetylations were mostly associated with memory for either spatial or fear learning. Altogether, these data suggest that behavior/experience-dependent changes differently regulate specific acetylation modifications of histones in the hippocampus, depending on whether a memory trace is established or not: tagging of H3K9K14 could be associated with perception/processing of testing-related manipulations and context, thereby enhancing chromatin accessibility, while tagging of H2B N-terminus tail and H4K12 could be more closely associated with the formation of memories requiring an engagement of the hippocampus.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetylation
  • Amino Acids / genetics
  • Amino Acids / metabolism*
  • Animals
  • Fear / physiology
  • Gene Expression Regulation
  • Hippocampus / metabolism*
  • Histones / genetics
  • Histones / metabolism*
  • Male
  • Maze Learning / physiology
  • Memory / physiology
  • Rats
  • Rats, Long-Evans
  • Space Perception / physiology


  • Amino Acids
  • Histones

Grants and funding

This work was supported by CNRS, INSERM, University of Strasbourg, ANR (ANR-12-MALZ-0002-01 to ALB) and granted by associations that the authors warmly thank: FRM-Alsace (to JCC and ALB), Ligue Européenne Contre la Maladie d’Alzheimer (LECMA project #10702 to ALB), Alsace Alzheimer 67 (to ALB and Dr. F. Blanc [FB], HUS, Strasbourg, France), as well as France Alzheimer Haut-Rhin (to JCC). OB received salary support from the LECMA, FORNASEP (to FB). RN and MAM were recipients of a doctoral fellowship from the French government, and RN received additional salary support from the LECMA. AS has been supported by the Fondation Unistra-don Pierre Fabre and ANR-12-MALZ-0002-01. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.