NOVA scienceNOW: Epigenetics
Students make a model of
chromatin and use it to show how chemical tags that bond to the chromatin can
influence its uncoiling.
Students will be able to:
the difference between genetics and epigenetics.
that the structure of chromatin includes DNA and histones coiled together.
how chemical tags that attach to the chromatin help the chromatin uncoil.
describe how chemical tags (i.e., an
epigenetic factor) play an important role in enabling DNA to be
"read" by enzymes and transcribed into messenger RNA.
- copy of the "Epigenetics" student handout
- colored, fine-tipped permanent marker
- ballpoint pen
lengths of thin (i.e., small-diameter) rubber surgical tubing, each 24 inches
long (1/8-inch rubber bungee cord can be used as a substitute)
small binder clips (3/4-inch size)
- packaging tape or duct tape, 2 inches in width
For students to grasp the basics of epigenetics, they will
need an understanding of DNA and its structural chemistry in the chromosome.
Consequently, this lesson is appropriate for a high school biology class in
which students have had some exposure to the fundamentals of DNA and RNA.
However, as the lesson's theme is epigenetics rather than DNA, the
lesson's goal is for students to be able to explain the difference
between genetics and epigenetics and to describe the role epigenetic factors
play in enabling DNA to be "read" by enzymes and transcribed by
In the field of epigenetics, scientists study how
chemical tags attach themselves to DNA or to the structures surrounding the
DNA. These chemical tags can control gene expression, silencing or activating
genes. Because these chemical tags are independent of the DNA sequence itself,
they are considered to be epigenetic factors. Epigenetic researchers examine
the role this silencing or activation of genes might play in cell
differentiation, cell development, disease, and heredity.
is a highly relevant area, offering scientists new ways to investigate many
fundamental questions about life, health, and disease. For example, how does a
single fertilized egg cell differentiate into over 200 cell types? How do
exposures to nutrients, toxins, pollutants, and other environmental agents
affect gene expression? These questions are at the core of much of
today's cutting-edge research and technology in such fields as health
care, medicine, pharmacology, fertility, and the management of environmental
activity, students build a model showing that DNA is enclosed in a histone
cushion to form chromatin, the basic component of a chromosome. They use the
model to demonstrate one way that methyl groups can bind to the chromatin,
enabling it to uncoil to expose the DNA. The activity should clarify the
meaning of the term epigenetics and suggest why researchers from many fields are so keenly
interested in learning more about the interaction between genetics and
Depending on how familiar
your students are with DNA and RNA, you might want to review DNA's
structure and the processes of transcription and translation. For example, have
students list three facts they can recall about DNA and RNA. Then ask students
to share their facts and develop a class list on the board or on a flip chart.
Also, discuss how the coiling of DNA around the histone proteins enables nearly
two meters-worth of DNA to fit into a microscopic cell nucleus!
Demonstrate how DNA is coiled into a
double helix. Before class, prepare a set of two tubes representing DNA. Mark
these tubes as described in Steps 1a and 1b on the Student Handout. Tape the
ends. Invite two students to help you in a demonstration. Have each helper take
a taped end of the tubing and face one another. Ask them to twist the tubes
into a spiral. Point out that, after just a few twists, the tubing forms into a
Demonstrate that DNA's double helix is itself
arranged into a secondary spiral. Have the students continue to twist. The
tubing will begin to knot up. Have the helpers pull lightly, maintaining gentle
outward pressure while still slowly twisting the tubing. The knots should begin
to organize into a thick spiral. The structure you are aiming for is a neat,
tight, thick spiral. Make sure the class understands what the model shows: (1)
the DNA double helix; and (2) the double helix itself is twisted into a
Add a histone strand and twist the three tubes into a
secondary spiral. Uncoil the DNA model and add the third piece of tubing. (It
does not matter where the third tube is in relation to the others, as long as
it is neatly alongside the other two.) Tape the three tubes together at the
ends. Tell students that chromosomes are made of more than just DNA—the
DNA is coiled around proteins called histones. Together, the histone proteins
and DNA form the chromatin. Chromatin, in turn, forms the chromosome. Once
taped together, the three lengths of tubing represent a section of chromatin.
Have the helpers repeat the twisting. Invite observations from the class about
the appearance of the three tubes. Make sure the class understands what the
model shows: (1) chromatin is made of DNA and histones; and (2) the chromatin
is twisted into a secondary spiral. (Tell students that in this model, the
third surgical tube [i.e., the one with dots or stripes] represents
chromatin's histone proteins. As with the two tubes, the three tubes will
also twist into the second spiral of knots. Point out how the inclusion of the
third tube as well as the twisting makes the sequence of letters [i.e., the
DNA's sequence of nucleotides] hard to read.)
Discuss how coiling makes it hard to read the DNA but
offers other advantages. Explain that the secondary level of coiling permits
the chromatin to be densely packed, enabling two meters-worth of DNA to fit
into a cell's nucleus. See if students can identify a major problem with
this arrangement. Ask:
When your body needs to make a protein, how can the genetic instruction hidden
in this coil of chromatin get "read"? Record the ideas on the board.
(When coiled, the DNA's sequence of nucleotides cannot easily be read.
Consequently, the instructions for protein synthesis are unavailable, and
enzymes cannot read the DNA to begin the process of transcription. When the
chromatin is in its tightly coiled state, the chromosomes are inactive—no
transcription [or protein synthesis] can take place.)
Have students make
their own models. Divide your class into groups of three or four students and
distribute the materials. Have each group follow the steps on the Student
Handout, in which they make their own chromatin model and use it to show how
chemical tags (i.e., epigenetic factors) can uncoil segments of the chromatin.
Then have them answer the questions at the end of the Student Handout.
Review how epigenetic
factors uncoil the chromatin. After students have finished, discuss the Handout
questions and students' answers.
Student Handout Questions
Why can it be difficult for enzymes to "read"
DNA base pairs in a coiled nucleosome?
nucleosome the DNA strand is wound onto the histone proteins the way a thread
is wound onto a spool. Furthermore, the nucleosomes are themselves coiled. All
the winding, twisting, and coiling make it essentially impossible for the
transcription enzymes to read a complete sequence of base pairs (i.e., a gene).
In your own words, explain the process of how methyl tags
(represented by the binder clips) help chromatin uncoil to reveal the base pairs
in a nucleosome.
methyl groups attach to particular sites on the tightly coiled chromatin,
specific parts of the chromatin (i.e., the nucleosomes) uncoil, revealing
segments of base pairs (i.e., the genes). Once the genes are revealed, it is possible
for messenger RNA to be transcribed.
How are methyl groups examples of an epigenetic factor?
groups originate outside the nucleus. They pass through the nuclear membrane
and attach at activation sites on the histones in the chromatin. The chromatin
affected by these methylated activation sites unravels, enabling transcription
of the genes in this section of the chromatin.
What would happen if methyl groups stayed attached to the
nucleosome forever and kept it continuously open?
be overproduction of a particular compound synthesized by that stretch of DNA.
Such an overproduction might be related to cancer-like processes.
List some ways that a nucleosome stuck in
"continuous reading" mode might become unstuck.
the methyl groups. If the groups cannot be removed, remove the segment
containing the groups (i.e., the strip with the two clips attached).
List some strengths and weaknesses of this
activity's model of the DNA–chromatin complex.
1) The relative sizes of the molecules are not accurately represented by the
rubber tubing. Specifically, the DNA strand is very fine and narrow compared to
the much larger histone protein core molecules. 2) In real life, the substances
coil in patterns different from those of the model tubing—the DNA is
almost like a fine double thread wound around the much more bulky histone
proteins. These histone proteins, in turn, resemble spools that are connected
to each other.
Strengths: 1) Rubber tubing
provides a usable representation of the components of chromatin and their
respective three-dimensional relationship with each other. 2) The secondary
coiling pattern creates a reasonable representation of the nucleosome. 3) Both
of these characteristics help to show how more than two meters of DNA can fit
into the nucleus of a microscopic cell.
Why might high-level exposures in early life to factors
that lead to the accumulation of methyl groups have health consequences much
later in life?
The accumulation of chemical tags, such as methyl groups,
that can stick to the histones or DNA might affect cellular repair mechanisms,
causing them to break down or become less effective.
epigenetics-related resources, including a streamed version of the show, an
audio slide show about how the epigenome produces differences, and an Ask the
Expert area where site visitors can ask researcher Randy Jirtle questions about
a well-written overview, with a clear diagram, of the connection between
epigenetic factors and disease in humans.
Network of Excellence
a brief yet informative overview of the field of epigenetics.
Network of Excellence
a brief, clear overview of epigenetics, with quotes from various researchers,
followed by a series of accessible descriptions of different topics in
Functions of Chromatin Modifications
how epigenetic-mediated dynamic changes in chromatin structure affect gene
expression, cell lineage commitment, and cancer development.
Hopkins Epigenetics Center in the Institute for Basic Biomedical Sciences
a basic introduction with an overview of epigenetics presented in lay terms.
Concepts and Connections
Neil Campbell, Jane Reece, Martha Taylor, and Eric Simon. Pearson/Benjamin
overview of genetics, DNA, RNA, and other related basic information; written at
level appropriate for high school.
C. David Allis, Thomas Jenuwein, Danny Reinberg, and Marie-Laure Caparros. Cold
Spring Harbor Press. 2007.
an up-to-date technical scientific collection of papers with useful overviews.
Cell's Second Act" by
Richard Saltus. HHMI
Bulletin, 19 (1), February, 2006.
researchers' efforts to understand nuclear reprogramming to revert adult
cells to medically useful embryonic stem cells.
"DNA Is Not Destiny" by Ethan Watters
science of epigenetics rewrites the rules of disease, heredity, and identity.
A historical overview" by
Robin Holliday. Epigenetics,
1:2, 76–80, 2006.
Offers a brief history of the field of epigenetics.
Takes the Spotlight: Decoding the environment's role in development and
Christen Brownlee. Science
News, 169 (25), June 2006.
current research and gives an accessible overview of epigenetics.
The "Epigenetics" activity aligns with the following National
Science Education Standards (see
Science Standard C
- The cell
- The molecular basis of heredity
Science Standard E
Science and Technology
- Understandings about science and technology
Science Standard F
Science in Personal and Social Perspectives
- Personal and Community Health
Classroom Activity Author
by John Glyphis, Ph.D., MPA. Glyphis is a biologist who consults on and writes
about science in education and public policy.