Epigenetics refers to heritable changes in gene expression that do not involve changes to the underlying DNA sequence. Experiments with genetically identical mice and rats showed that differences in maternal diet during pregnancy can lead to epigenetic changes that affect offspring phenotypes such as fur color, weight, and disease risk, without changing genotypes. Studies also demonstrate that early life experiences like levels of maternal care can induce epigenetic changes in brain development and stress response in offspring. These findings have potential applications for detecting and preventing health issues influenced by epigenetic factors during fetal development and across generations.

1. Epigenetics
Alexandra Steinruck
Biology 101-07
April 21, 2013

2. How is it possible for a mother to give birth to identical twins, but only one has
medical problems? Why are children good at the same sports and activities as their
parents? How can two genetically identical mice look like polar opposites? These
questions can all be answered by one thing: epigenetics.
Scientists have found that there is more to an organism than just its genes.
Epigenetics is the study of how one changes an organism’s phenotype, without
changing the genotype. The prefix “epi-” means on or above, so epigenetics refers to
things that happen on top of the genes. Epigenetics changes the activity or expression
of a gene; it does not rewrite the DNA (genetic code).
Conrad Waddington (1905-1975) is credited with coining the term epigenetics in
1942 as “the branch of biology which studies the causal interactions between genes and
their products, which bring the phenotype into being”. The term epigenetics appears in
literature as far back as the mid 19th century. However, the general idea dates back to
Aristotle (384-322 BC). He believed in something called epigenesis: the development of
individual organic form from the unformed. This view was the main argument against
our having developed from miniscule fully-formed bodies. (McVittie, 2006)
Even now, the extent to which we are preprogrammed versus environmentally
shaped is continually debated. The field of epigenetics has emerged to bridge the gap
between nature and nurture. In the 21st century epigenetics is most commonly defined
as ‘the study of heritable changes in genome function that occur without a change in
DNA sequence‘.

3. In 1866, Gregor Mendel showed that pea plants inherit physical and other traits
from their parents according to very precise laws of nature. In 1910, Thomas Hunt
Morgan showed that genes exist on chromosomes, and in 1952 Martha Chase and
Alfred Hershey showed that DNA within a gene carries traits from parent to child.
(Pochron, 2011, pg.1) When someone tells you, “It’s in your genes,” they’re saying that
the part of your chromosome responsible for your quirk matches that part of the
chromosome on your equally quirky parent. Recent research has now shown that this
saying is not quite true. Inherited traits have more to do with what is “on” your genes
than what is “in” them.
In 2003, Dr. Randy Jirtle and his colleagues at Duke University were looking
ways to affect phenotypes without changing the actual DNA of an organism. They
started testing on mice, specifically, “identical twin” mice. Dr. Jirtle decided to look at
the effects of a pregnant mother’s diet on the health of the mother’s fetus. He had
genetically identical mothers implanted with genetically identical zygotes. After
impregnating the mice, he continued to watch and care for them. The mothers were
kept in the same environment and received the exact same treatment in every area
except one. The scientist changed the diet that he fed to each mouse. (Pochron, 2011,
pg.2)
To the first group of mothers, he fed a diet that would turn on a particular gene in
their offspring, the Agouti gene. The second group of mice received a vitamin rich diet
that turned off the Agouti gene in their offspring. The Agouti gene controls fur color and
the ability to feel full after eating. When the gene was turned on in the first group of

4. mice, they grew into orange adults that never felt full. They ate all the time, but never
reached the point of feeling satisfied. The second set of mice, whose mothers received
the vitamin rich diet, grew into brown adults and developed a feeling of fullness after
eating. (Pochron, 2011)
In addition to the differences in color and eating habits, the orange mice’s weight
causes it to have greater potential for diabetes and cancer. Despites these differences,
the two groups of mice still had the same genes. Through this experiment, Dr. Jirtle
and his colleagues were able to show the power of epigenetics changes.
So, how exactly do epigenetic changes occur? Genes contain the recipe for
proteins. Every time a gene is turned on, it makes its particular protein. But how much
— if any — of the protein a gene makes and when it makes the protein can be altered
by the addition or deletion of methyl groups. Methyl groups are chemical clusters each
made of one carbon and three hydrogen atoms. They latch onto DNA near a gene.
Methyl groups then act like switches, turning a gene on or off. (Pochron, 2011)
Changes in diet and stress and other environmental factors can flip these chemical
clusters on or off, affecting the activity of the neighboring gene. Epigenetic factors
include both spatial patterns, such as the arrangement of DNA around histone proteins
(chromatin), and biochemical tagging. (McVittie, 2006)
There are hundreds of different kinds of cells in our bodies. Although each one
derives from the same starting point, the features of a neuron are very different from
those of a stomach cell. With some 30, 000 genes in the human genome, silence is just
as important as activity, if not more so. As cells develop, their fate is determined by the

5. selective use and silencing of genes. This process is subject to epigenetic factors.
DNA methylation patterns play a role in all sorts of phenomena where genes are
switched on or off, from the color of a flower to the growth of cancerous tumors.
Failure to silence genes can produce hazardous effects. Too little DNA
methylation can alter the arrangement of chromatin. This affects which genes are
silenced after cell division. On the flip side, too much methylation can squash the work
done by protective tumor suppressors and DNA repair genes. Such epimutations have
been observed in a wide range of cancers. (McVittie, 2006)
So, why are gene switches so flippable? Maybe the answer lies in common
sense rather than in lab studies. Environments change constantly — forests change to
grasslands, and grasslands change to deserts. Environments within and around our
cells change due to things such as parasites and viruses. Social environments change
too: A nurturing environment can become hostile simply by a stroke of bad luck. No
matter how we look at it, humans and other organisms live in constantly changing
environments.
On the other hand, an organism’s genome — or set of genetic instructions —
doesn’t change quickly. For example, humans now look a lot like humans from 200,000
years ago, even though parents pass on a jumbled mixture of genes to their offspring.
How does something as steady as a genome cope with something as changeable as
the environment? Perhaps epigenetics is the answer.
Moshe Szyf at McGill University believes that epigenetics may offer a way to help
our unchanging genes cope with sudden changes in our environment. (Pochron, 2011)

6. Changing what’s on our genes appears to be easier than changing what’s in them. This
may help explain how life so readily adapts to our ever-changing environment.
In order for epigenetics changes to be more permanently established, they must
be passed down through reproduction. In October 2010, Margaret Morris and her
colleagues at the University of New South Wales in Sydney, Australia began an
experiment to test if this is possible. Morris used healthy, identical male rats for her
experiment. She put half of them on a high fat diet, and the other half received a
regular rat diet. The rats that ate the high fat diet grew into obese adults and
experienced diabetes. The other half of the rats grew into average size adults without
medical complications. (Pochron, 2011)
The rats were then all paired with genetically identical females to mate with.
Morris wanted to see if the daughters would inherit any epigenetic changes from their
fathers that would cause them to be obese. Standard genetic research at the time
would suggest that this would not occur. What she found was even more interesting.
None of the daughters experienced obesity. While this was expected, the other findings
were not. Daughters of the fat rats experienced medical issues associated with obesity.
“Female baby rats looked as though they were on their way to becoming diabetic. They
couldn’t produce enough insulin,” Morris stated. (Pochron, 2011)
Insulin is a hormone needed for the body to use glucose — also known as blood
sugar. Glucose is the body’s energy source. A shortage of insulin or the body’s inability
to use insulin effectively causes diabetes, a very serious disease.

7. Genetic changes obviously did not cause the daughters’ insulin problems,
because the scientists had used genetically identical parents. Instead, fat dads created
sperm cells with different methyl patterns. Daughters inherited their father’s epigenetic
changes. And because of changes in methyl patterns on the genes, the daughters also
inherited their dads’ health problems.
Through these experiments and more, scientists have discovered that diet is a
very important factor for epigenetic changes. Also, not only the diet that a person eats,
but the food and drink their parents ingested before and during the time that person was
in the womb can change that person’s gene expression. Scientists have also
discovered that smoking, drinking alcohol, and aging can create in methyl groups as
well. (Cloe, 2011)
Researchers were also curious as to whether something other than diet could
change an organism’s epigenetics. In 2004, Michael Meaney and his colleagues at
McGill University in Montreal decided to test the effects of behavior on epigenetic
changes. (Pochron, 2011)
Previous research had already shown that differences in how an infant rat is
mothered can affect how it responds to fear stimulants later in life. Many rat mothers
lick their newborns to show care. However, others do not lick their offspring. Research
has shown that rats that were licked as infants grow up to be adults that are braver
when placed in stressful situations. Rats that are not licked as infants are much more
fearful and timid later in life.

8. Meaney believed that these results were due to epigenetic changes, and he was
right. His team found distinct differences in methyl patterns in the brains cells of the
licked and non-licked rat babies. The licking from the mothers switched on methyl
groups that controlled how the offspring responds to stress. This showed that the
behavior of one animal can affect the epigenetics of another.
Meaney decided to take his experiment one step further. He wanted to see if it
was possible to change the rats’ epigenetics as adults medically. In 2007, he injected
chemicals into the brave rats to wipe out methyl markers that were affected by the
mother’s licking/non-licking. The experiment was a success. The scared rats became
brave. (Pochron, 2011) This was one of the greatest discoveries in the field of
epigenetics. This discovery gives hope to the idea that we can change gene expression
in humans to help cure diseases.
The ability to chemically flip methyl switches can help treat human diseases. For
example, doctors can cure specific forms of leukemia (cancer of the blood or bone
marrow) by using chemicals to flip methyl switches. Other scientists, including Randy
Jirtle, are exploring the role of epigenetics in diseases like schizophrenia (an illness
marked by deterioration of the thought processes), depression (an illness characterized
by a feeling of such sadness that the sufferer can’t live a normal life) and autism (an
illness that makes it difficult to communicate with other people).
Jirtle says, “I want to find the genes in humans that are involved in brain
development, which, as a consequence, are involved in just about every neurological

9. disorder we have.” (Pochron, 2011) Once Jirtle finds the genes, he’ll look for the methyl
groups that affect them. He believes he can find cures this way.
Many diseases have a known genetic component, but may be modified by
epigenetics. Epigenetic features like DNA methylation are much more viable targets for
treatment because it’s much easier to change the way DNA is methylated than to
change the underlying DNA sequence.
One way scientists are looking at changing epigenetic features is during fetal
development. Researchers at Mount Sinai School of Medicine have found that
epigenetic marks on human placentas change from the first trimester of pregnancy to
the third, a discovery that may allow clinicians to prevent complications in pregnancy.
Previously, it was believed that epigenetic programming is permanently established at 2
weeks after fertilization. (Mt. Sinai Hospital, 2010)
"Our research shows that there are several 'windows of opportunity' during
pregnancy to detect risks and also change pregnancy outcomes that may arise later,"
said the study's senior investigator, Men-Jean Lee, MD, Associate Professor,
Obstetrics, Gynecology and Reproductive Science, and Preventive Medicine, Mount
Sinai School of Medicine. "We have developed an assay that can allow clinicians to
diagnose problems early enough to potentially prevent conditions such as preeclampsia
and fetal growth restriction." (Mt. Sinai Hospital, 2010)
In a pregnant woman, the placenta contains a group of genes, known as
"imprinted" genes, which regulate fetal growth. In healthy fetal development, one copy
of these genes is normally active and the other copy is silent. Loss of imprinting (LOI)
occurs when both sets of genes are reactivated, and is an indicator of potential

10. complications such as preeclampsia and fetal growth restriction. (Mt. Sinai Hospital,
2010)
An estimated 10 percent of pregnancies are complicated by fetal growth
restriction. This restriction increases the risk of stillbirth, cerebral palsy, feeding
intolerance, and failure to thrive. Preeclampsia, a condition characterized by high blood
pressure and swelling during pregnancy, affects between 7 and 10 percent of pregnant
women. (Mt. Sinai Hospital, 2010)
In 2010, using an LOI assay, the research team assessed LOI at the first
trimester in 17 placentas and at full term in 14 different placentas. The surprising
results showed that more LOI occurred in the first trimester than at full term. This was
the first study conducted that compared LOI in the first trimester to LOI of full-term
placentas. With the knowledge of the changeability of LOI, biomarkers can now be
developed to test if a pregnancy is destined to develop preeclampsia or fetal growth
restriction. If these markers are detected early enough, doctors may be able to help the
mothers prevent the diseases.
A 2009 study by University of Utah researchers found that poor nutrition during
pregnancy affects the epigenetics of rats, stunting their growth and increasing their risk
of cardiovascular disease, diabetes, delayed development and obesity. The study
suggests that the same effects may occur in humans. (Cloe, 2011)
Nutrition is the most important intrauterine environmental factor that alters
expression of the fetal genome and may have lifelong consequences. This
phenomenon, termed “fetal programming,” has led to the recent theory of “fetal origins

11. of adult disease.” Namely, alterations in fetal nutrition and endocrine status may result
in developmental adaptations that permanently change the structure, physiology, and
metabolism of the offspring, thereby predisposing individuals to metabolic, endocrine,
and cardiovascular diseases in adult life. Animal studies show that both maternal under
nutrition and over nutrition reduce placental-fetal blood flows and stunt fetal growth.
(Wu, 2004)
Impaired placental syntheses of nitric oxide and polyamines (key regulators of
DNA and protein synthesis) may provide a unified explanation for intrauterine growth
retardation in response to the 2 extremes of nutritional problems with the same
pregnancy outcome. There is growing evidence that maternal nutritional status can
alter the epigenetic state (stable alterations of gene expression through DNA
methylation and histone modifications) of the fetal genome. This may provide a
molecular mechanism for the impact of maternal nutrition on both fetal programming
and genomic imprinting. Promoting optimal nutrition will not only ensure optimal fetal
development, but will also reduce the risk of chronic diseases in adults. (Wu, 2004)
To sum it up, the studies of both animals and humans have made it increasingly
clear that proper epigenetic regulation of both imprinted and non-imprinted genes is
important in placental development. Its disturbance, which can be caused by various
environmental factors, can lead to abnormal placental development and function with
possible consequences for maternal morbidity, fetal development and disease
susceptibility for the offspring later in life.
In Conclusion, epigenetics is a growing field of research in which there is much
potential for increased health benefits. Epigenetic changes can occur due to diet,

12. exercise, alcohol, smoking, and behaviors of the person or others around them. These
changes can also be passed down to offspring from both the father and the mother.
Scientists have found that epigenetics can be modified in many ways. One way
is to watch for epigenetic markers in embryonic development in order to help prevent
diseases from occurring in the offspring. Another way to create an epigenetic change is
with the implantation of chemicals later in life. This could help by turning off certain
genes responsible for things such as cancer, depression, schizophrenia, autism, and
other diseases. More research is needed to find which genes are responsible for which
characteristics of a human, but there is much potential for this field.

13. References
Cloe, Adam. (2011, September 9) What Consequences Can Arise From Poor Nutrition
During Pregnancy? Livestrong. Retrieved March 6, 2013, from
http://www.livestrong.com/article/539539-what-consequences-can-arise-from
poor-nutrition-during-pregnancy/
Lewin, Benjamin. Jones and Bartlett Publishers (2007). Epigenetic effects can be
inherited. Retrieved March 7, 2013, from
http://bioscience.jbpub.com/cells/MBIO52322.aspx
McVittie, Brona. Epigenome NoE. Epigenetics? Retrieved March 6, 2013, from
http://www.epigenome.eu/en/4,27,0
Mount Sinai Hospital / Mount Sinai School of Medicine (2010, April 15). Changes in
fetal epigenetics found throughout pregnancy. Science Daily. Retrieved March 6,
2013, from http://www.sciencedaily.com/releases/2010/04/100414152129.htm
Nelissen, E.C. Department of Obstetrics and Gynecology, Research Institute Growth &
Development (GROW), Center for Reproductive Medicine, Maastricht University
Medical Centre. Epigenetics and the placenta. NCBI. Retrieved March 7, 2013,
from http://www.ncbi.nlm.nih.gov/pubmed/20959349
Pochron, Sharon. (2011, September 21). What’s on your genes? Tiny genetic switches
create big differences. Retrieved March 7, 2013, from
http://www.sciencenewsforkids.org/2011/09/what%e2%80%99s-on-your-genes/
Wu, G., Bazer, F. W., Cudd, T. A., Meininger, C. J., and Spencer, T. E. (2004). The
American Society for Nutritional Sciences. Maternal Nutrition and Fetal

14. Development. Retrieved March 7, 2013, from
http://jn.nutrition.org/content/134/9/2169.full