Epigenetics

Definition

Epigenetics (from the Greek: επί – over, outside of, or around the genome) is the study of trait variations caused by external or environmental factors that switch genes on and off and affect how cells read genes. Epigenetic research seeks to describe dynamic alterations in the transcriptional potential of a cell outside of the changes to the DNA sequence (the genotype).
The term also refers to the changes themselves: functionally relevant changes to the genome that do not involve a change in the nucleotide sequence. Gene expression can be controlled through the action of repressor proteins that attach to silencer regions of the DNA. These epigenetic changes may last through cell divisions for the duration of the cell’s life, and may also last for multiple generations even though they do not involve changes in the underlying DNA sequence, instead, non-genetic factors cause the genes to behave differently. (definition and diagram – Wikipedia)

Epigenetic_mechanisms

 

Discussion

Epigenetics is the contemporary study of how the environment influences gene expression both within and, through heritable changes in DNA, beyond the lifetime of an organism. The idea that organisms can inherit environmentally acquired characteristics is, however, the old idea of Lamarckian inheritance. In 1809, Jean-Baptiste Lamarck suggested that an organism would acquire traits through adapting to its environment, and that these traits would then be inherited by its offspring. Lamarck’s theory was overlooked in favor of Darwin’s natural selection theory of evolution, as the two explanations appeared at the time to be mutually exclusive, but the advent of epigenetics has made it possible for these theories to be reconciled. “Epigenetics” literally means “above the genes,” and is the means by which the environment “marks” the genes, dramatically or subtly, changing their level of expression either transiently or for our lifetime, or, through inheritability, throughout our children’s and grandchildren’s lifetimes. A formal definition of epigenetic events proposed by Adrian Bird is: “the structural adaption of chromosomal regions so as to register, signal or perpetuate altered activity states”. This definition encompasses the broad remit of epigenetic marks from transient, where the epigenetic mark ascribed by the environmental adaption lasts only a few hours, to heritable, where the environmental effects last over a generation. The brain-derived neurotrophic factor (BDNF) gene, implicated in psychiatric disorders and learning and memory, is subject to both short- and long-term epigenetic marking in rodents. For example, following the favorable social experience of being reared in a communal nest, mice challenged with one hour in a mildly stressful novel environment generate hippocampal BDNF faster than mice raised in a standard nest, as a result of an epigenetic mark on the BDNF gene. However, rat pups subjected to a rat equivalent of childhood maltreatment are epigenetically marked by this experience, reducing the level of BDNF in their pre-frontal cortex throughout their adult life. The offspring of these rats also carry the same epigenetic mark on their BDNF gene even when they have been cross-fostered to non-maltreating mothers. Thus, epigenetics, the mechanisms by which our genes record or adapt to the environment, can shape gene expression over a few minutes, an hour, or a lifetime, and can even shape the gene expression pattern of the next generation. It is even possible for genes to “remember” an event and make a contingency plan for its recurrence, as in the case of the corticotropin-releasing hormone gene of rat pups. In response to maternal deprivation, the promoter region of this gene is epigenetically marked. Later, following a stressful experience in adulthood, the pre-recorded epigenetic mark leads to a hypersensitive stress response, observed as a more actively transcribed corticotropin-releasing hormone gene and increased levels of the stress hormone corticosterone.

There are three main types of epigenetic modification: DNA methylation, histone modification, and translational regulation by micro RNA.

(Adapted from: Peckham, H. 2013. Epigenetics: The dogma-defying discovery that genes learn from experience. The Neuropsychotherapist, 1, 1. doi: 10.12744/ijnpt.2013.0009-0020

Clinical Relevance:

  • Many animal studies of epigenetics have looked at the impact of early maternal care on the hypothalamic-pituitary-adrenal (HPA) axis or, put more simply, the stress axis. Early pre-natal stress in mice has been epigenetically linked to enduring changes in HPA axis reactivity and a depressive phenotype in male offspring. Early post-natal stress has also been linked to enduring epigenetic changes that alter the reactivity of the HPA axis. (Peckham, 2013)
  • Human studies have also found a correlation between early childhood experiences of trauma and neglect with changes in gene expression. Reciprocally, enriched positive environments can elicit different and positive genetic expressions. (Peckham, 2013)
  • The clinical relevance of epigenetic findings is the understanding that enriched environments can change genetic expression, possibly reversing negative environmental impacts on a person, enhancing resilience and neural plasticity.

Resources:

Baylin, J. 2013. Behavioral Epigenetics and Attachment. The Neuropsychotherapist, 3. doi: 10.12744/tnpt(3)068-079

Peckham, H. 2013. Epigenetics: The dogma-defying discovery that genes learn from experience. The Neuropsychotherapist, 1, 1. doi: 10.12744/ijnpt.2013.0009-0020