Question

a) Describe why drugs that cause epigenetic changes can be used to treat chronic depression or stress.

b) Using a suitable example, explain what a metastable epiallele is.

Answer 1

a) In the absence of stress, the chromatin status of BDNF (brain derived neurotrophic factor) is in an open configuration and the expression of BDNF at a basal level: moderate H3 acetylation levels and almost no H3-K27 dimethylation. Under chronic stress/depression: closed chromatin state with high H3-K27 dimethylation leading to inhibition of BDNF expression. Some HDAC inhibitors (sodium borate) have been used as antidepressants. Even though they do not remove the repressive H3-K27 dimethylation marks specifically, they lead to a more open form of the promoter by reducing deacetylation, which allows the expression of BDNF

b) A metastable epiallele is an allele that can be epigenetically modified in a variable and reversible manner. This can change the phenotype of genetically identical cells. The agouti viable yellow (A(vy)) epiallele is an example of a metastable epiallele. Expression of the Agouti gene is influenced by the DNA methylation status of an upstream retroelement.