Epigenetic Control

  • Epigenetic control is determined by whether a gene is being expressed or not
  • It is the attachment or removal of epigenetic marks to or from the DNA/histone proteins
  • Epigenetic marks do not alter the DNA sequence
  • Epigenetic marks do alter the accessibility for enzymes and other proteins needed for transcription to interact with and transcribe the DNA
  • Epigenetic changes to gene expression is vital in many normal cellular processes
  • Epigenetic change can be the result of environmental factors

Inheritance

  • As organisms inherit the DNA sequences from parental most of the epigenetic markers on the DNA are removed between generations
  • However, some epigenetic markers are left on (accidently) and therefore express of these genes can be affected by environmental changes that had affected the parents/grandparents

Controlling Gene Expression

  • Increased Methylation of DNA
    • Methylation is the addition of a methyl group to the DNA for a gene
      • Methyl groups are an epigenetic marker
    • Methyl group is always attached to CpG site
      • CpG site is where cytosine and guanine bases are next to each other in the DNA. They are linked by a phosphodiester bond
    • Increased methylation results in a alteration to the DNA structure
    • Therefore, transcriptional enzymes cannot interact with the gene – the gene is not expressed
  • Decreased acetylation of histones
    • Histone proteins wrap DNA around to form chromatin
      • Chromatin can be highly condensed or relatively less condensed
      • It is how condensed the chromatin is does it affect the accessibility of the DNA and whether or not it can be expressed
    • Histones can be epigenetically modified by the addition/removal of acetyl groups
      • Aceytl groups are an epigenetic marker
    • When histone acetylation occurs the chromatin is less condensed – which allows genes to be expressed
    • When acetyl groups are removed from histones the chromatin becomes highly condensed – which prevents genes to be expressed
    • Histone deacetylase is responsible for the addition/removal of the acetyl from the histone

Treating Disease

  • Epigenetic changes are reversible – therefore it makes them more suitable for drugs which target the disease. These types of drugs are designed to counteract the epigenetic change
    • g. increased methylation is an epigenetic change that can lead to a gene being switched off
    • Drugs that stop DNA methylation can sometimes be used to treat the disease
  • Decreased acetylation of histones could also lead to genes being not expressed
  • Issues faced is developing a drug to counteract an epigenetic change:
    • All cells will be affected due to the nature of targeting epigenetic sites so drugs have to be highly specific