The name is derived from epi- (Greek: επί- over, outside of, around) combined with genetics, literally meaning being “over genetics”. Epigenetics is the study of heritable changes in gene activity which are NOT caused by changes in the DNA sequence. While the idea that factors other than changes in DNA can affect development was discussed almost a century ago (called “epigenesist” by CH Waddington), epigenetics is now more often considered to be changes to DNA that don’t involve changes in the DNA sequence itself. Moreover the term epigenetics can also be used to describe the study of stable, long-term alterations in the transcriptional potential of a cell that are not necessarily passed on to the next generation. Though this last point is contentious – some scientists believe the definition of epigenetics is modifications to DNA that are passed onto the next generation of either daughter cells (mitosis) or germ cells (meiosis).

So unlike simple genetics, where mutations affect the genotype by changing letters of the DNA alphabet (the four nitrogenous bases adenine (A), guanine (G), cytosine (C), and thymine (T)), epigenetic changes that cause changes in gene expression have other roots.

So if the DNA is not changed, what is changed instead? Generally this involves chemical modifications around DNA that cause gene expression to be changed, most often silenced.  These modifications can act as an extra layer of information and, in the brain, are thought to play an important role in learning and memory, as well as in age-related cognitive decline.

The results of a study by researchers at the Salk Institute for Biological Studies  published in Science show that the landscape of DNA methylation – a particular type of epigenetic modification that adds a methyl group (CH₃) – is highly variable in brain cells during certain developmental stages. These new findings help us understand how information in the DNA of brain cells is controlled from early fetal development to adulthood.

With humans having exceptionally complex and large brains (larger than any other mammal in relation to body size) it is clear that building and shaping a healthy brain is the product of a long process of development. We know that the front-most part of our brain (the prefrontal cortex) for example is a critical part of the executive system, which refers to planning, reasoning, and judgment. The brain accomplishes all of this through the interaction of specialized cells such as neurons and glia, the brain’s communication specialists. We know that these cells have distinct functions.

But now epigenetics tells us what gives these cells their individual identities! It all depends on how each cell expresses the genetic code. And this how is done by epigenetic modifications, fine-tuning which genes are turned on or off without changing the DNA sequence, and thus subsequently helping to distinguishing different cell types.

The Salk scientists found that the patterns of DNA methylation undergo dynamic rearrangements in the frontal cortex of mouse and human brains during a time of development when synapses, or connections between nerve cells, grow rapidly. By comparing the exact sites of DNA methylation throughout the genome in brains from infants through adults, the researchers noticed that one form of DNA methylation can be found in neurons and glia from birth. However, a second form of DNA methylation that is almost exclusive to neurons accumulates as the brain matures, becoming the most prevalent form of DNA methylation in adult human neurons.

Teachers and child development experts have long known about natural breakage points in a child’s development. These new results can help us to understand how those points occur as the intricate DNA landscape of brain cells develops during the key stages of childhood.

What is the mechanism of DNA methylation? As mentioned above, the genetic code in DNA is made up of four nitrogenous bases A, T, C, and G. DNA methylation typically occurs at so-called “CpG sites,” where C (cytosine) sits next to G (guanine) in the DNA alphabet. Interestingly about 80–90% of CpG sites are methylated in human DNA. Moreover, in human embryonic stem cells and induced pluripotent stem cells, a type of artificially derived stem cell, DNA methylation can also occur when G does not follow C, called “non-CG methylation.” Originally, scientists thought that this type of methylation disappeared when stem cells differentiate into specific tissue-types. This latest study found this is not the case in the brain, because non-CG methylation appears after cells differentiate, and they usually differentiate during childhood and adolescence when the brain is maturing. What this finding underlines is that at the time the neural circuits of the brain mature, a parallel process of large-scale reconfiguration of the neural epigenome takes place.

The study also included the first comprehensive maps of how DNA methylation patterns change in the mouse and human brain during development (see insert). Future research can explore how changes in methylation patterns may be linked to human diseases, including psychiatric disorders like schizophrenia, depression, and bipolar disorder.

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Further reading:

You can even get a quick PowerPoint podcast on the research!

https://dl.dropboxusercontent.com/u/1421283/Epigenome_Movie.mov

The first comprehensive maps of epigenetic changes in the brain known as "DNA methylation," a chemical modification of a cell's DNA that can act as an extra layer of information in the genome. Credit: Lister et al, 2013.

Well what do I mean by lasting changes? Research has shown that depending on what your mother eats may influence your genes and health in the long run. The gene agouti is found in humans and mice. The agouti/melanocortin system is an important regulator of body weight homeostasis. Mouse studies have shown that when the agouti gene is not methylated the result is obese yellow coated mice which may be at risk for cancer and diabetes. When the gene is methylated mice are brown, of normal weight and size. The only difference between the two types of mice is the methylation control on the agouti gene. In parallel experiments were carried out where yellow female mice were fed a methyl enriched diet; the offspring grew to be normal weight, size and were brown in color and remained so for the rest of their adulthood. This study identified that an individual’s wellbeing is not only determined by what they eat but also what their parents ate.

References
Nutrition and the epigenome. Retrieved February 8, 2012, from http://learn.genetics.utah.edu/content/epigenetics/nutrition/

This may help to answer many questions.  How can we have so many different types of cells and they all carry the same genetic information?  How is it possible for one identical twin to develop cancer while the other does not?  Can we use this control of the gene expression to help cells that may have lost their way?

It is amazing to think that just about all of the cells of the human body has the same DNA.  The full genetic profile with all of the instructions on how to make a human is in almost every cell.  When most students come through the DNA Learning Center, many of them think that there is different DNA inside of these cells.  That red blood cells have different DNA than bone cells and nerve cells.  One way this is done is through the interaction of small methyl groups (-CH₃) that get added to the DNA molecule, which can help to silence a gene that is not needed in some type of cell or at some point of development.  This is a epigenetic “tag” because there is no change to the sequence of DNA, it is just whether or not there is access to the DNA.  The methyl groups that get added make the cell unable to activate that gene.

This addition of methyl groups, called methylation, also can change throughout the course of our life.  So as we get older the interaction of these groups with our DNA can change.  So even with identical twins, who are born with the same DNA, their epigenetic “tags” can vary and occur independent of one another.  And even more, certain lifestyle choices and experiences throughout the life of a person can change the epigenetic profile of an individual.  And then this gets passed on to our children.  So even what a mother eats while pregnant can affect the tags that get passed to their child.  This ultimately will affect the expression of genes in the child.

And now we are using this information to help treat disease, such as cancer.  So if a gene is turned on that shouldn’t be, could we add methyl groups to that section of the DNA to turn it off?  This has started being used as a new therapy for the treatment for certain cancers.