Diverse and dynamic DNA modifications in brain and diseases

Hum Mol Genet. 2019 Nov 21;28(R2):R241-R253. doi: 10.1093/hmg/ddz179.

Abstract

DNA methylation is a class of epigenetic modification essential for coordinating gene expression timing and magnitude throughout normal brain development and for proper brain function following development. Aberrant methylation changes are associated with changes in chromatin architecture, transcriptional alterations and a host of neurological disorders and diseases. This review highlights recent advances in our understanding of the methylome's functionality and covers potential new roles for DNA methylation, their readers, writers, and erasers. Additionally, we examine novel insights into the relationship between the methylome, DNA-protein interactions, and their contribution to neurodegenerative diseases. Lastly, we outline the gaps in our knowledge that will likely be filled through the widespread use of newer technologies that provide greater resolution into how individual cell types are affected by disease and the contribution of each individual modification site to disease pathogenicity.

Publication types

  • Research Support, N.I.H., Extramural
  • Review

MeSH terms

  • Adenosine / analogs & derivatives*
  • Adenosine / chemistry
  • Adenosine / metabolism
  • Alzheimer Disease / genetics
  • Alzheimer Disease / metabolism*
  • Animals
  • Ataxia / genetics
  • Ataxia / metabolism
  • Brain / metabolism
  • Chromatin / chemistry
  • Chromatin / enzymology*
  • Chromatin / genetics
  • Chromatin / metabolism
  • Cytosine / chemistry
  • Cytosine / metabolism*
  • DNA / metabolism
  • DNA Methylation / genetics
  • Epigenesis, Genetic*
  • Histones / metabolism
  • Humans
  • Mice
  • Neurodegenerative Diseases / metabolism
  • Parkinson Disease / genetics
  • Parkinson Disease / metabolism*

Substances

  • Chromatin
  • Histones
  • N6-methyladenosine (m6A)
  • Cytosine
  • DNA
  • Adenosine