Recent discoveries

have shed light on how

genes alternate
biotech 101
between silent and
active states. These Epigenetics
activity patterns appear flipping the genetic “switch”
to be susceptible to
Epigenetics – Activating genes to begin the protein-
environmental What you need to know: making process is a key area of study in
Genes are specific segments of DNA genetics and biotechnology. By identify-
influences, with serious
n

that contain the instructions for creat- ing the signals that turn genes “on” and
ing proteins. “off”, investigators hope to understand
health consequences not only gene function under normal
n Genes can switch between active
conditions, but also how improper on/
that stretch across (directing protein production) or silent
(no protein produced) phases. off signaling may lead to disorders such
generations. as cancer, diabetes, heart disease and
n Patterns of activation and silencing,
obesity.
known as the epigenome, exist across
all the genes in a cell. The study of To illustrate the importance of gene
these patterns is called epigenetics. activity, consider another set of “twins”
– in this case two laboratory mice. At
n Changes in the epigenome do not
birth, these twins, while genetically
change a gene’s sequence, but rather
identical, look nothing alike. One has
its activity status.
the brown-colored fur typically associat-
n The environment can alter the epi- ed with mice while the other has yellow
genome, changing the activity level
fur. As the yellow mouse, also called an
of genes. These changes may raise or
“agouti mouse” grows to adulthood, it
lower the risk for developing diseases
like cancer, obesity and diabetes. becomes obese, often developing dia-
betes and various types of tumors. The
n Some environmental factors, such as agouti gene responsible for these differ-
diet, not only change an individual’s
ences produces a protein that regulates
epigenome, but appear to influence
a number of other genes. Typically, the
the epigenome of future generations.
agouti gene makes this regulatory pro-
n The environmental triggers that alter tein only briefly during mouse develop-
the epigenome and lead to disease are
ment. This quick period where the agou-
only beginning to be discovered.
ti gene is “on” results in the brown coat
color. If the agouti gene is always “on”

I
Want more information:
www.pbs.org/wgbh/nova/science- dentical twins (who share the same however, the other genes are continu-
now/3411/02.html genetic information) are exactly alike ally activated. Consequently, the mice
Epigenetics – – or are they? While they generally look develop yellow fur, obesity and tumors.
a recent NOVA program providing an
alike when young, as twins age obvious Amazingly, the difference between the
excellent overview of epigenetics and
the agouti mouse experiments differences often emerge. The differ- healthy brown mouse and its overweight
ences may be due to the varied environ- yellow twin is not a change in the DNA
discovermagazine.com/2006/ ment of each twin – for example, one sequence of the agouti gene. Instead,
nov/cover
may lift weights and become very mus- the difference stems from a tiny molecu-
DNA Is Not Destiny –
an article from the November 11, cular while the other never exercises and lar tag made of carbon and hydrogen.
2006 issue of Discover magazine that gains weight. Recent advances in the In the healthy mice, this tag, called a
not only discusses the agouti mouse, relatively new field of epigenetics sug- methyl group, binds to the agouti gene,
but a number of epigenetic findings gest an additional role for the environ- silencing it during the majority of devel-
in other organisms, including humans
ment in health and disease by altering opment (figure 1). No methyl groups are
 the activity of particular genes. present at the agouti gene of the yellow
hudsonALPHA institute for biotechnology
 figure 1 ing patterns. Preliminary findings
suggest that environment altera-
tions to the epigenome change an
individual’s risk for disease. Similar
to the mouse studies, evidence in
humans indicates some epigenetic
changes may be “remembered”
across multiple generations.
Epigenetics is still in its infancy
and a complete understanding of
these mechanisms is many years
away. Regardless, it appears clear
that epigenetic modifications can
influence disease susceptibility,
potentially lasting through several
generations. Future studies will be
aimed at identifying all epigenetic
modifications, clarifying the en-
vironmental triggers that modify
the epigenome, and determining
mice and the gene remains active. The environmental influence that occurred which genes are most susceptible
cells of living creatures contain millions many years previously. to the changes. On the distant hori-
of methyl tags, working as switchboard In humans, there is also evidence of zon, knowledge of the triggers and
operators to control which genes are ac- epigenetic modification. A handful of their genetic targets offers the pos-
tive and which are silenced. genetic diseases, known as “imprinting sibility of early disease diagnosis,
Methyl groups represent just one of disorders” have been linked to improper as well as the hope that the epig-
the epigenetic mechanisms cells use methylation of key developmental genes. enome may someday be modified
to oversee gene activity. These mecha- Studies of identical twins suggest that at to treat the disease once symptoms
nisms account for the very specific pat- birth, twins share similar epigenomes. have appeared, or even prevent its
terns of silencing and activation that ex- As they age and are exposed to differ- occurrence altogether. n
ist in every cell. For example, skin cells ent diets and environments, the twin’s – Dr. Neil Lamb
have an activation pattern of genes dif- epigenomes become markedly different, director of educational outreach
ferent from muscle or nerve cells, based leading to altered activation and silenc- HudsonAlpha Institute for Biotechnology
on which genes have been silenced. It is
this unique combination of genes that figure 2
are “on” which leads to the individual
shape and specific work performed by
each cell type.
The epigenetic patterns can be ad-
justed as cells grow and divide by alter-
ing the environment around the cells.
If a female yellow mouse is fed a diet
rich in methyl groups before and dur-
ing her pregnancy, she will produce
primarily brown-furred newborn mice
with a silenced agouti gene (figure 2).
The extra methyl groups protect the
offspring from obesity and other adult-
onset heath problems. Surprisingly, this
protection extends beyond the offspring
and into the next generation of mice (the
grandchildren of the initial yellow-furred
mother). This finding suggests that epi-
genetic modifications can be passed
across generations – a “memory” of 
hudsonALPHA institute for biotechnology