Brief Look into Epigenetics

James Keyhani
11/18/15

Epigenetics studies how external factors such as an organisms environment and behavior
can influence their genetic activity other than their DNA sequence. Epigenetic processes can
switch genes on or off and determine which proteins are transcribed. These epigenetic changes
have been linked to diseases such as cancer or mental retardation. The other characteristic of
epigenetics is that these changes can be passed down to descendants. In the case of
Caenorhabditis Elegans (type of nematode) scientists found evidence for epigenetic inheritance
of longevity by a means of genetic crossing. This study suggests that traits that promote
longevity or disease can be inherited by a means of epigenetics.
In epigenetics there are three processes that can alter gene expression. The first process is
known as DNA methylation. In this process, a group of atoms called a methyl group attach
themselves to the DNA. The ability to figure out the amount of DNA methylation helps
researchers determine whether a gene is switched off or on. The second epigenetic process
involves histones. Histones are proteins that bind to DNA. They bend and coil the long DNA
molecules to form chromosomes. Many chemicals can modify histones, thus altering gene
expression. The third epigenetic process involves small molecules of RNA. RNA molecules can
interact with protein or DNA to alter and regulate the activity of certain genes. As the genome
dictates the heredity of organisms, the epigenome focuses on the epigenetic activity which
dictates to the genome what to express based on the organisms environmental influences.
The concept of epigenetics has been a topic of discussion for several centuries, however
the term was not coined until the 1940s. The idea that genes are influenced by factors outside the
genome is much older and can be linked to late nineteenth-century discussions of whether the
nucleus or the cytoplasm controlled development. There was also earlier nineteenth-century
discussions of whether the sperm or egg provided the primary material for development. The
even earlier discussions of the eighteenth-century discussed concepts of organismal structure as
either preformed which means arising by unfolding in its simplest terms or arising gradually by
epigenesis.
The study of how organisms develop can be traced back to the 4th century BCE and from
the literature of the Greek philosopher Aristotle. He developed a way of explaining how animal
embryogenesis worked and the concept became known as preformation which is described as the
development of traits and phenotypic characteristics that are preformed within the sperm or egg
and epigenesis which was described as the successive differentiation of feature during
development and formation of the adult form. Until the 20th century preformation was the
preferred method of explaining how development worked. Epigenesis would not become
epigenetics as we know it until the 1970s.
After studying the genetic features of fruit flies during embryogenesis, British
embryologist Conrad Waddington needed a way to describe the role of genes and genetic control
in and over embryonic development, so in 1942 Waddington he coined the term epigenetics.
Waddington defined epigenetics as casual interactions between genes and their products which
bring the phenotype into being. However it was not until the 1970s and 1980s that it became an
established discipline. At that point in time they discovered the biological processes behind
epigenetics such as DNA methylation and its relationship to cancer. The first evidence for
transgenerational epigenetic inheritance would be until the 1990s. Today scientists are studying
the relationship between epigenetics and disease, epigenetic inheritance, and epigenetic therapy.
Although epigenetics is a part of everyday life and required if we want to function
properly, it can also be responsible for the damage done to our bodies like causing disease to
occur. If any of the three systems that control epigenetic activity were to be disrupted it can cause

abnormal activation or silencing of genes. Alterations of this kind have been associated with
cancer, syndromes involving chromosomal instabilities, and mental retardation. The first human
disease to be linked to epigenetics was cancer, in 1983. Researchers found that diseased tissue
from patients with colorectal cancer had less DNA methylation than normal tissue from the same
patients. Because methylated genes are typically turned off, loss of DNA methylation can cause
abnormally high gene activation by altering the arrangement of chromatin. On the other hand,
too much methylation can undo the work of protective tumor suppressor genes (1).
In the study Transgenerational epigenetic inheritance of longevity in Caenorhabditis
elegans, scientist take a look at how chromatin modifiers regulate lifespan in several
organisms, raising the question of whether changes in chromatin states in the parental generation
could be incompletely reprogrammed in the next generation and thereby affect the lifespan of
descendants (3). The scientists determined that deficiencies in H3K4me3 a type of chromatin
modifier, and a functioning germline resulted increased lifespan. Thus, manipulation of specific
chromatin modifiers only in parents can induce an epigenetic memory of longevity in
descendants (3).
Scientists are finding new ways to put this understanding of epigenetics to work through
the use of epigenetic therapy. With epigenetic therapy scientists can combat diseases that are
epigenetically influenced such as cancer. Epigenetic diseases can be reversed unlike genetic
mutations. The most popular treatments aim to alter the DNA methylation or histone acetylation.
Inhibitors of DNA methylation can reactivate genes that have been silenced. Two examples of
these types of drugs are 5-azacytidine and 5-aza-2-deoxycytidine. These medications work by
acting like the nucleotide cytosine and incorporating themselves into DNA while it is replicating.
After they are incorporated into DNA, the drugs block DNMT enzymes from acting, which
inhibits DNA methylation (1).
Drugs that are designed to modify histones are known as histone deacetylase inhibitors.
Histone deacetylase are enzymes that remove the acetyl groups from DNA, which compresses
chromatin and stops transcription. Blocking this process with histone deacetylase inhibitors turn
on gene expression. The most common histone deacetylase inhibitors include phenylbutyric acid,
SAHA, depsipeptide, and valproic acid.
Even though this a very exciting field which hopefully will offer more promising results
in the future people still need to be cautious of using epigenetic therapy. This is due to the
epigenetic processes and changes being so unpredictable during treatment. Therefore successful
epigenetic treatments must be selective to irregular cells because activating gene transcription
in normal cells could make them cancerous, so the treatments could actually activate the very
disorders they are trying to counteract. Essentially what this means is that epigenetic therapy is
difficult to use as treatment at the moment because every persons epigenome is unique, so not
every medication researchers attempt to use to combat the disease will work because of the
numerous factors.
Epigenetics also offers some very important contribution to biology. It seems that it may
be able increase our understanding of evolution and offer an additional mechanism that could
influence it. According to a study that was conducted by Michael Skinner and several others,
they found that mate preference could be influenced at the molecular level by environmental
epigenetics and could have a role in evolutionary biology. How the scientists came to this
conclusion is by conducting experiments with an environmental compound (the fungicide
vinclozolin) which was found to promote mating and modify mating preferences for several
generations on rats. The scientist in their conclusion described their evidence to appear as a neo-

Lamarckian concept that facilitate neo-Darwinian evolution (8). Essentially the scientists are
suggesting that epigenetics is a mechanism for the environment to impact phenotypic variation
and natural selection (8).
After going over various aspects of epigenetics such as its history, describing what it is,
its relationship with disease, epigenetic inheritance, the solutions to combatting epigenetic
disease, and its relationship to biology one gets a feeling of fullness and understanding of the
subject. However one also realizes that this barely scratches the surface of what this field is
capable of and what research already exists today. This field seems to be very exciting and will
hopefully offer more promising results and explanations in the future.

Citations
1. Danielle Simmons (2008). Epigenetic Influences and Disease. Nature Education. Web Journal.

2. Epigenetics. (2015). Funk & Wagnalls New World Encyclopedia, 1p. 1..

3. Greer et. al. (2011). Transgenerational epigenetic inheritance of longevity in Caenorhabditis

elegans. Nature, 479(7373), 365-371.

4. Hall, B. K., & Hallgrimsson, B. (2011). Epigenetics : Linking Genotype and Phenotype in
Development and Evolution. Berkeley: University of California Press. pg. 9-13.

5. Daxinger, L., & Whitelaw, E. (2010). Transgenerational epigenetic inheritance: More

questions than answers. US National Library of Medicine National Institutes of Health, 16231628.

6. Weinhold, B. (2006). Epigenetics: The Science of Change. Environ Health Perspect

Environmental Health Perspectives.

7. Rasool et. al. (2015). The role of epigenetic in personalized medicine: challenges and
opportunities. BMC Genomics, 161-8.

8. Skinner et. al. (2014). Gene bionetworks involved in the epigenetic transgenerational
inheritance of altered mate preference: environmental epigenetics and evolutionary biology.
BMC Genomics, 15(1), 1-38.