Changes to histone modifications following prenatal alcohol exposure: An emerging picture

Alcohol. 2017 May:60:41-52. doi: 10.1016/j.alcohol.2017.01.005. Epub 2017 Feb 4.

Abstract

Epigenetic mechanisms are important for facilitating gene-environment interactions in many disease etiologies, including Fetal Alcohol Spectrum Disorders (FASD). Extensive research into the role of DNA methylation and miRNAs in animal models has illuminated the complex role of these mechanisms in FASD. In contrast, histone modifications have not been as well researched, due in part to being less stable than DNA methylation and less well-characterized in disease. It is now apparent that even changes in transient marks can have profound effects if they alter developmental trajectories. In addition, many histone methylations are now known to be relatively stable and can propagate themselves. As technologies and knowledge have advanced, a small group has investigated the role of histone modifications in FASD. Here, we synthesize the data on the effects of prenatal alcohol exposure (PAE) on histone modifications. Several key points are evident. AS with most alcohol-induced outcomes, timing and dosage differences yield variable effects. Nevertheless, these studies consistently find enrichment of H3K9ac, H3K27me2,3, and H3K9me2, and increased expression of histone acetyltransferases and methyltransferases. The consistency of these alterations may implicate them as key mechanisms underlying FASD. Histone modification changes do not often correlate with gene expression changes, though some important examples exist. Encouragingly, attempts to reproduce specific histone modification changes are very often successful. We comment on possible directions for future studies, focusing on further exploration of current trends, expansion of time-point and dosage regimes, and evaluation of biomarker potential.

Keywords: Alcohol; Epigenetics; FASD; G9a; Gene expression; H3K27me3; H3K9ac; H3K9me2; Histone.

Publication types

  • Review

MeSH terms

  • Acetylation
  • Alcohol Drinking / adverse effects
  • Alcohol Drinking / genetics
  • Alcohol Drinking / metabolism*
  • Animals
  • Brain / metabolism*
  • Chromatin Assembly and Disassembly*
  • DNA Methylation
  • Disease Models, Animal
  • Epigenesis, Genetic
  • Female
  • Fetal Alcohol Spectrum Disorders / genetics
  • Fetal Alcohol Spectrum Disorders / metabolism*
  • Gestational Age
  • Histocompatibility Antigens / metabolism
  • Histone Acetyltransferases / metabolism
  • Histone-Lysine N-Methyltransferase / metabolism
  • Histones / genetics
  • Histones / metabolism*
  • Humans
  • Maternal Exposure / adverse effects*
  • Methylation
  • Pregnancy
  • Prenatal Exposure Delayed Effects*
  • Protein Processing, Post-Translational

Substances

  • Histocompatibility Antigens
  • Histones
  • EHMT2 protein, human
  • Histone-Lysine N-Methyltransferase
  • Histone Acetyltransferases