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NOVA scienceNOW: Epigenetics

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Before Watching

1. Review DNA and chromosomes. As a class, review the following definitions:

   • DNA: a double-stranded molecule that carries a cell's genetic information and is found in the cells of all living organisms.

   • Chromosome: A tightly coiled macromolecule of DNA and its associated proteins. Chromosomes contain many genes. Sexually reproducing organisms have two of each chromosome, one from each parent. Organisms vary in the number of chromosomes they have. For example, humans have 46, dogs have 78, mosquitoes have 6, a potato has 48, and a pea plant has 14.

   • Genome: The entire set of hereditary factors in a haploid set of chromosomes.

   Show the class a three-dimensional DNA model. Have students identify the two strands that make up DNA, the sugar-phosphate backbone, the individual nucleotide bases, and the nucleotide base pairs. To help students better understand the way DNA affects a person's traits, have students look at sets of paired chromosome from individuals with genetically caused conditions, such as Down syndrome, Huntington's disease, Klinefelter's syndrome, Tay-Sachs disease, and Jacobs Syndrome. Compare these to a set of paired chromosomes from an unaffected individual. (Suggested resource: pathology.washington.edu/galleries/Cytogallery/
   main.php?file=human%20karyotypes)

2. Play a word game exploring the meaning of "epi." Have students use a standard or medical dictionary to identify words beginning with the prefix epi, which means "above," "in addition to," or "outside." Give student pairs vocabulary terms and definitions (all mixed up). Have pairs work together and match each word to its correct definition. Review the terms as a class, and then have students brainstorm the meaning of epigenome and epigenetics.

   • Epigenome: Above or outside the genome. In a sense, the epigenome is like clothing around the DNA. For example, chemical groups alter the expression of the DNA by binding to the DNA as well as to the histones around the DNA.

   • Epigenetics: The study of changes in gene expression that do not involve changes in the genetic code (i.e., the DNA sequence) because they lie outside of the genome (i.e., the DNA). In a sense, epigenetics is the study of the genome's "clothing".

3. Write similes and analogies that compare the genome to the epigenome. Brainstorm similes that show the relationship of the genome to the epigenome. For example, scientists in the program refer to the genome (i.e., DNA) as being "like the hardware of a computer" and the epigenome as being "like computer software." The DNA needs the epigenome to function properly, just as the computer needs the software to function properly.

   Divide the class into teams, and write on the board, "______is/are to the genome (i.e., DNA) as ______ is/are to the epigenome." As a class, brainstorm analogy examples such as:

   • Keys of a piano are to the genome as fingers are to the epigenome.

   • Wires in an electric circuit are to the genome as switches are to the epigenome.

   Then ask teams to generate other ways of showing the relationship of the genome to the epigenome. Have teams share their work.

4. Discuss "nature versus nurture" questions about identical and fraternal twins. On the board, diagram how identical and fraternal twins compare genetically. Explain that with identical twins, a single fertilized egg splits into two genetically identical parts, each having the same DNA. With fraternal twins, two separate eggs are fertilized. Point out that identical twins are genetically identical, while fraternal twins are only as genetically similar as typical siblings are. Divide the class into groups and have groups discuss, research, and prepare responses to the following nature/nurture-related questions:

   1. Which type of twins, identical or fraternal, always shares the same blood type? (Identical)

   2. Should blood type be used to determine whether a set of twins is identical or fraternal? Why or why not? (No, fraternal twins may have the same blood type.)

   3. Do identical twins always have the same handedness? Why or Why not? (Not always, right or left handedness isn't entirely determined by genetics.)

   4. Do identical twins always have the same eye color? (Almost always, though some diseases can change eye color.) Hair color? Explain your answer. (Natural hair color is almost always the same, but hair can be dyed.)

   5. Do identical twins always have the same fingerprints? Why or why not? (Not necessarily, some identical twins have mirror-image prints.)

   6. Would identical or fraternal twins prefer the same type of music? Explain your answer. (Not necessarily. Answers will vary.)

   7. With which type of twins will both individuals always be born as the same sex? (Identical)

   8. Would twins always weigh the same at birth? Why or why not? (No, they may have received differing amounts of nutrients.)

   9. Is it best for scientists to study identical or fraternal twins to learn about the impact of the environment on genes? (Identical, because they have the same genome.)

After Watching

1. Analyze models for epigenetic factors. The segment displays an animation of the relationship between DNA and the epigenome, such as the histone proteins and methyl groups. Replay the animation for students and discuss how DNA's structure can be altered by epigenomic factors that expose (often by acetylation) or hide (often by methylation) different areas of the genome.

   Use a skein of yarn to model coiled DNA, and attach a washer to the loose end. Hold the skein so that the washer pulls the loose end down. Have students identify the epigenetic factor. (The washer—it's not part of the "DNA") Which part of the DNA was hidden and unavailable for transcription but is now available? (The length pulled from the skein by the washer—the exposed part)

2. Brainstorm models for stem cells, the genome, the epigenome, and cancer. In the program, one explanation for how some types of cancer arise is through errors when stem cells overwork to replace tissue. Discuss with students that a stem cell can develop into any of the body's cell types. One function of stem cells is regeneration and repair of damaged tissue. Stem cells that keep dividing because they can't shut down their own growth may be one way cancer develops.

   Discuss stem cells with students, using a well-stocked kitchen could be used as a metaphor for stem cells. The genome would be all the ingredients; the epigenome would be opening a cabinet door to retrieve a particular ingredient; and cancer would be adding too much of one or more ingredients in a recipe. Other metaphor examples include a cookbook, telephone, CD player, or computer. As a class, brainstorm similar metaphor models. Then have student teams correlate each metaphor to stem cells, the genome, the epigenome, and cancer. Have teams share their metaphors and analysis.

3. Draw a cartoon or write a poem or song. Over centuries, many scientists have contributed to our understanding of heredity and DNA. Have student teams research one of the scientists listed below and, using a cartoon, poem, or song, present that scientist's contribution. Have teams include when the scientist lived, where he or she worked, and at least one significant contribution he or she made to advance our understanding of heredity, DNA, and/or genetics.

   • Charles Darwin (1809–1882): Wrote On the Origin of Species in 1859. He proposed the theory of natural selection and suggested that adaptive traits were inherited.

   • Gregor Mendel (1822–1884): Studied peas and other plants. Found that traits are carried by discrete units (later, these were termed "genes") and that there are rules of inheritance.

   • Alfred Hersey (1908–1997) and his assistant Martha Chase: Showed in 1952 that DNA, rather than proteins, carries genetic information. He won a Nobel Prize for this work.

   • Rosalind Franklin (1920–1958): Isolated and took X-ray crystallography images of DNA, setting the stage for Watson and Crick to make their breakthrough insight into the structure of DNA.

   • James Watson and Francis Crick (Watson 1928–, Crick 1916–2004): In 1953, determined the structure of DNA. Both scientists won a Nobel Prize for this work.

   • The Human Genome Project (Developed in the late 1980s/early 1990s): Many scientists continue to work on this project, sequencing the human genome to better understand such diseases as Alzheimer's. Early results include the discovery that each of the body's cells contains more than three billion nucleotide units. About one percent of the genome (clustered in as few as 30,000 genes) seems to be used for transcription.

4. Write a twin-study proposal. Review with students why scientists use identical twins to study the effect of the environment on the epigenome (and ultimately on health). (Because identical twins have the same genetic makeup, scientists can study how differences in lifestyle influence twins' epigenomes and their health.) In a way, the environment "talks" to us through the epigenome. Lifestyle differences can be reflected in the epigenome. Have students brainstorm lifestyle differences that identical twins may have that could influence their epigenome, and, by extension, their health. On the board, record students' ideas. Possible ways identical twins' epigenomes could be different include:

   • Twins live in different geographic locations. One twin lives close to where there is heavy use of pesticides and one does not. Scientists could study the impact of pesticides on health (kidney disease) and on the epigenome.

   • One twin smokes and one doesn't. Scientists could study the impact of smoking on health (lung disease) and on the epigenome.

   • One twin eats a vegetarian diet and one doesn't. Scientists could study the impact of a particular diet on health and the epigenome.

   • One twin has a particular kind of cancer. Scientists could study the role of the environment in that type of cancer by carefully looking at differences in where and how each twin lives.

   • One twin works as a police officer and one as a yoga instructor. Scientists could study the impact of stress on health conditions such as heart attacks or ulcers; they could also study changes in the epigenome.

   As a class, review the core elements of a scientific proposal. For example:

   • Have students carefully define a question.

   • Isolate one variable.

   • Identify the twin who is the focus of the experiment and the one who is the control.

   • Have students consider other factors that could influence data or results.

   • Make sure students consider the ethics involved in doing their study.

   Have students review the list of ways identical twins could have different epigenomes, and choose a health-related question that could be addressed in a twin study. Divide the class into teams, and have each one choose a question from this list to further address in a proposal (each team takes a different question). Have teams write a proposal for studying their question to learn more about whether the environment could have influenced the epigenome and could have been the main contributor to a particular health factor. Then have teams share their completed proposals with the class.

Web Sites

NOVA scienceNOW
www.pbs.org/nova/sciencenow/3411/02.html
Offers 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 epigenetics.

Environmental Health Perspectives
www.ehponline.org/members/2006/114-3/focus.html
Provides a well-written overview, with a clear diagram, of the connection between epigenetic factors and disease in humans.

Epigenome Network of Excellence
epigenome-noe.net/aboutus/epigenetics.php
Offers a brief yet informative overview of the field of epigenetics.

Epigenome Network of Excellence
epigenome.eu/en/1,1,0
Presents a brief, clear overview of epigenetics, with quotes from various researchers, followed by a series of accessible descriptions of different topics in epigenetics.

The Functions of Chromatin Modifications
www.hhmi.org/research/investigators/zhang.html
Explains how epigenetic-mediated dynamic changes in chromatin structure affect gene expression, cell lineage commitment, and cancer development.

Johns Hopkins Epigenetics Center in the Institute for Basic Biomedical Sciences
www.hopkinsmedicine.org/press/2002/November/epigenetics.htm
Provides a basic introduction with an overview of epigenetics presented in lay terms.

Books

Biology: Concepts and Connections
by Neil Campbell, Jane Reece, Martha Taylor, and Eric Simon. Pearson/Benjamin Cummings, 2006.
Provides overview of genetics, DNA, RNA, and other related basic information; written at level appropriate for high school.

Epigenetics
by C. David Allis, Thomas Jenuwein, Danny Reinberg, and Marie-Laure Caparros. Cold Spring Harbor Press. 2007.
Compiles an up-to-date technical scientific collection of papers with useful overviews.

Articles

"A Cell's Second Act" by Richard Saltus. HHMI Bulletin, 19 (1), February, 2006.
www.hhmi.org/bulletin/feb2006/features/cell2.html
Describes researchers' efforts to understand nuclear reprogramming to revert adult cells to medically useful embryonic stem cells.

"DNA Is Not Destiny" by Ethan Watters
discovermagazine.com/2006/nov/
The new science of epigenetics rewrites the rules of disease, heredity, and identity.

"Epigenetics: A historical overview" by Robin Holliday. Epigenetics, 1:2, 76–80, 2006.
cnru.pbrc.edu/pdf/history_of_epigenetics.pdf
Offers a brief history of the field of epigenetics.

"Nurture Takes the Spotlight: Decoding the environment's role in development and disease" by Christen Brownlee. Science News, 169 (25), June 2006.
www.sciencenews.org/articles/20060624/bob8ref.asp
Reviews current research and gives an accessible overview of epigenetics.