Epigenetic Changes Associated with the Expression of Amyotrophic Lateral Sclerosis (ALS) Causing Genes

Neuroscience. 2018 Oct 15:390:1-11. doi: 10.1016/j.neuroscience.2018.08.009. Epub 2018 Aug 19.

Abstract

Neurodegenerative disorders, including Amyotrophic Lateral Sclerosis (ALS), have been associated to alterations in chromatin structure resulting in long-lasting changes in gene expression. ALS is predominantly a sporadic disease and environmental triggers may be involved in its onset. In this respect, alterations in the epigenome can provide the key to transform the genetic information into phenotype. In this paper, we demonstrate that two modifications associated with transcriptional activation, namely dimethylation of lysine 4 on H3 tail (H3K4me2) and phospho-acetylation of serine 10 and lysine 14 on H3 tail (H3K14ac-S10ph), and two modifications associated to transcriptional repression, namely trimethylation of lysine 9 on H3 tail (H3K9me3) and DNA methylation are selectively altered in cellular and animal model of ALS. These results reinforce the idea that epigenetic therapy may represent a potential and attractive approach for ALS treatment.

Keywords: Amyotrophic Lateral Sclerosis; DNA methylation; FUS; SOD1; TDP43; histone posttranslational modifications.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amyotrophic Lateral Sclerosis / genetics*
  • Amyotrophic Lateral Sclerosis / metabolism*
  • Animals
  • Cell Line, Tumor
  • DNA Methylation
  • DNA-Binding Proteins / metabolism
  • Epigenesis, Genetic*
  • HEK293 Cells
  • Histones / metabolism
  • Humans
  • Mice, Transgenic
  • Protein Processing, Post-Translational*
  • RNA-Binding Protein FUS / metabolism
  • Superoxide Dismutase-1 / metabolism

Substances

  • DNA-Binding Proteins
  • FUS protein, human
  • Histones
  • RNA-Binding Protein FUS
  • SOD1 protein, human
  • TARDBP protein, human
  • Superoxide Dismutase-1