Your Brain on Epigenetics

Scientists have debated the importance of nature vs. nurture for years. For the first time, however, both sides have shaken hands and acknowledged a tie. The burgeoning field of epigenetics has changed the way we view genes and how they are inherited.

Certain traits, like height and hair color can largely be explained through simple genetics: If both of your parents are tall with blond hair, chances are you will be too. However, not all genes are created equal and most traits are not controlled by a single gene. Instead, most traits, such as metabolism, personality, intelligence, and even many diseases, are much more complex and rely on the interactions of hundreds of different genes. The complexity doesn’t stop there either! If it did, then identical twins would be exactly the same; but they are not! Although they tend to be extremely similar, identical twins can still differ greatly in health and personality. This is because, although they carry an identical set of genes, their genes may be expressed at different levels. Genes are not simply turned “on” or “off” like a light switch, but instead function more like a dimmer switch with a dynamic range of expression. The amount that a gene is expressed can differ from one person (or twin) to another and can even fluctuate within a single individual. The mechanisms by which these kinds of changes take place are extremely complicated and are influenced by a variety of factors including one’s internal and external environment. Epigenetics is the study of these kinds of changes and the mechanisms behind them.

The best understood mechanism of epigenetic regulation is DNA methylation. In DNA, the cytosine base can be modified by the addition of a methyl-group , resulting in a “methylcytosine” (5mC). These modifications are predominantly found along the DNA in a “CpG” context(where a cytosine base is immediately followed by a guanine base).  “CpG” dense regions are often found before the actual gene sequence, in a region called a promoter. Within these promoter regions, 5mC marks modify the expression level of a gene by acting as an obstacle, hindering the necessary molecular machinery from accessing the DNA. In simple terms, when a promoter is methylated, the gene is considered to be inactive (or less active).

In addition to 5mC, there is another kind of modified cytosine base: hydroxymethylcytosine (5hmC). This modification occurs at a very low prevalence relative to 5mC but is much more abundant in the brain and central nervous system compared to any other tissues in the body. This discovery of 5hmC’s has lead to speculation about the possible importance of 5hmC in brain-specific functions. Indeed, in a study published last year by Khare et al., many genes containing 5hmC were found to be involved in synaptic plasticity.

Intriguingly, many epigenetic marks have been found to be heritable, being able to persist through many cell divisions and can even be conserved from parent to offspring! In another recent study, Mychasiuk et al. found that when male rats were subjected to chronic stress, they produced offspring with altered behavioral and developmental characteristics. These differences correlated with altered DNA methylation levels in the hippocampus and frontal cortex, suggesting that chronic stress in the father may have caused epigenetic changes resulting in altered gene expression in its offspring!

The macro-environment of our epigenetics includes maternal, paternal, and environmental influences, which interact in ways that researchers are only beginning to understand. The nervous system is vastly complex, and while a single, small epigenetic change might not leave a noticeable effect, several small changes — or a select few of the right changes in combination– can lead to potentially drastic changes in phenotypes of behavior, personality, development and disease. There are many unanswered questions regarding the implications of epigenetic regulation of the brain and researchers have barely began to scratch the surface.

~

References:

Khare T., Pai S., Koncevicius K., Pal M., Kriukiene E., Liutkeviciute Z., Irimia M., Jia P., Ptak C., Xia M. & Tice R. (2012). 5-hmC in the brain is abundant in synaptic genes and shows differences at the exon-intron boundary, Nature Structural & Molecular Biology, 19 (10) 1037-1043. DOI:10.1038/nsmb.2372

Mychasiuk R., Harker A., Ilnytskyy S. & Gibb R. (2013). Paternal stress prior to conception alters DNA methylation and behaviour of developing rat offspring, Neuroscience, 241 100-105. DOI:10.1016/j.neuroscience.2013.03.025

~

Written by Eliza Bacon.

Illustrations made by Jooyeun Lee, Ryan Jones, and Anita Ramanathan.