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What is Epigenetics?

Epigenetics means literally "above the genes” and refers to modifications in gene expression that do not involve changes in the DNA nucleotide sequence. Epigenetic changes may include:

  • Chemical modifications (e.g., methylation) to DNA or RNA
  • Chemical modifications to DNA associated proteins (e.g., histones)
  • Incorporation of histone variants which alter the chromatin conformation
  • mRNA degradation by microRNAs (~22 nucleotides-long RNA sequences)
Epigenetic modifications result from environmental influences. Overall, epigenetic changes either enhance or inhibit gene expression without altering the DNA sequence. Phenotypic outcome is dictated by the specific combination of epigenetic modifications.

Epigenetic mechanisms target DNA, histones and mRNA

Read the blog: The Epigenetics of Depression: How Psychological Stress Alters DNA

Epigenetics in Health and Disease

Epigenetic programs play a crucial role in many biological processes including embryonic development and cellular differentiation. For example, the genome of pluripotent cells is generally highly methylated while the process of differentiation is associated with a loss of DNA-methylation marks. Additionally, pluripotent cells generally have a greater incidence of chromatin in an open state, which is determined by specific histone modifications, while differentiated cells are more enriched in condensed chromatin. Epigenetic mechanisms have been also recently recognized to regulate autophagy, a homeostatic process controlling cellular components.

Abnormal frequency or location of epigenetic marks, often due to the aberrant function of DNA- or histone-modifying enzymes, has been associated with various disease states including cancer and neurodegeneration. For example, hypermethylation of tumor-suppressor genes has been identified as a pro-tumorigenic aberrant epigenetic mechanism.

Chromatin Modifiers: Major mechanisms inducing chromatin changes include

  1. DNA/RNA methyltransferases: add methyl groups directly to DNA or RNA nucleotides
  2. Histone modifiers: add or remove acetyl and methyl groups to histones within nucleosomes
  3. Chromatin remodelers: change the composition and positioning of nucleosomes

Learn more about Epigenetic Machinery