Epigenetic stability in the adult mouse cortex under conditions of pharmacologically induced histone acetylation

Brain Struct Funct. 2016 Nov;221(8):3963-3978. doi: 10.1007/s00429-015-1138-0. Epub 2015 Nov 2.

Abstract

Histone acetylation is considered a major epigenetic process that affects brain development and synaptic plasticity, as well as learning and memory. The transcriptional effectors and morphological changes responsible for plasticity as a result of long-term modifications to histone acetylation are not fully understood. To this end, we pharmacologically inhibited histone deacetylation using Trichostatin A in adult (6-month-old) mice and found significant increases in the levels of the acetylated histone marks H3Lys9, H3Lys14 and H4Lys12. High-resolution transcriptome analysis of diverse brain regions uncovered few differences in gene expression between treated and control animals, none of which were plasticity related. Instead, after increased histone acetylation, we detected a large number of novel transcriptionally active regions, which correspond to long non-coding RNAs (lncRNAs). We also surprisingly found no significant changes in dendritic spine plasticity in layers 1 and 2/3 of the visual cortex using long-term in vivo two-photon imaging. Our results indicate that chronic pharmacologically induced histone acetylation can be decoupled from gene expression and instead, may potentially exert a post-transcriptional effect through the differential production of lncRNAs.

Keywords: Epigenetics; Histone acetylation; RNA-seq; Synaptic plasticity.

Publication types

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

MeSH terms

  • Acetylation
  • Animals
  • Cerebral Cortex / metabolism*
  • Cerebral Cortex / physiology*
  • Dendritic Spines / physiology
  • Epigenesis, Genetic*
  • Frontal Lobe / metabolism
  • Frontal Lobe / physiology
  • Gene Expression Profiling
  • Hippocampus / metabolism
  • Hippocampus / physiology
  • Histones / metabolism*
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Neuronal Plasticity*
  • Occipital Lobe / metabolism
  • Occipital Lobe / physiology
  • Olfactory Bulb / metabolism
  • Olfactory Bulb / physiology
  • RNA, Messenger / metabolism

Substances

  • Histones
  • RNA, Messenger