8-2-8-epigenetics-and-disease

Epigenetics & disease

• Epigenetic therapies aim to reverse epigenetic changes to restore normal gene expression

• These treatments are promising because epigenetic changes are reversible, unlike mutations

• Epigenetic therapies are being explored for:

  • neurological diseases (e.g. Alzheimer’s, schizophrenia)

  • autoimmune diseases

  • metabolic conditions (e.g. diabetes)

  • infertility and developmental disorders

Epigenetic cancer treatment

• Cancer arises from uncontrolled cell division, often caused by mutations or incorrect expression of genes

• DNA in human tumour cells have changes in DNA methylation and histone acetylation which causes tumour suppressor genes to be silenced and oncogenes to be activated

  • This leads to deregulation of the cell cycle and the formation of tumours

• Epigenetic modifications are reversible, so they are targets for new cancer therapies

• Cancer treatments can involve drugs that reverse the epigenetic changes through the removal of acetyl and methyl tags

  • Removal of methyl groups from the DNA of tumour suppressor genes will enable the genes to be expressed

  • The proteins produced can then regulate the cell cycle and stop tumours forming from faulty or cancerous cells

  • Removal of acetyl groups from histone proteins attached to oncogenes causes the DNA to wrap more tightly, silencing these genes

  • Reducing the expression of oncogenes stops cancer, as faulty cells are able to die through apoptosis rather than continuing to replicate, causing cancer

• Other epigenetic cancer therapies include:

  • DNA demethylating agents:

    • These chemicals inhibit enzymes that add methyl groups (DNA methyltransferases).

    • The aim is to reactivate silenced tumour suppressor genes

    • E.g. Drugs like azacitidine used in some leukemias

  • histone deacetylase (HDAC) inhibitors:

    • These prevent histone deacetylation which maintains acetylation so that chromatin remains open

    • This results in increased expression of beneficial genes (like those inducing apoptosis)