Epigenetics is the study of how external factors and internal cellular signals can lead to changes in the packaging and processing of DNA sequences, thereby altering the expression of genes and traits. Exploring the epigenome introduces students to environmental influences on our genes and the complexities of gene expression. A supplemental curriculum module developed by the Genetic Science Learning Center (GSLC) at the University of Utah brings epigenetics to high school and undergraduate classrooms through a range of online and paper-based activities. We describe these activities and provide strategies for incorporating both introductory and more advanced materials that explore “cell memory,” epigenetic inheritance, nutrition, and emerging connections between the epigenome and behavior. Finally, we outline recent reach on student learning gains using the GSLC's epigenetics module and provide connections to the Next Generation Science Standards.

The DNA in each of our nucleus-bearing cells is identical unless it has undergone mutation. However, external factors and internal cellular signals can influence changes in the packaging and processing of these identical DNA sequences, thereby altering the expression of genes and traits. Epigenetics is the study of these changes and how they can lead to variation in gene expression without changes in the DNA nucleotide sequence (the Greek root epi means “over” or “above”).

In eukaryotes, two types of epigenetic modifications, DNA methylation and histone modification, influence whether genes are turned “on” or “off.” Gene activation – and, thus, transcription – is blocked when DNA methyltransferases bind methyl molecules to DNA at sites where a cytosine and a guanine are linked by a phosphate. Normal CpG methylation silences certain genes during egg and sperm formation. Most of these tags are reset after fertilization, but imprinted genes keep their epigenetic tags so that only one copy of the gene is active. This imprinting is required for normal development. Imprinting errors can result in diseases such as Prader-Willi and Angelman syndromes.

About 40% of mammalian genes contain a section in their promoter region, called a “CpG island,” where >55% of base pairs are CG. Methylation levels in these islands are normally very low, but human cancer cells show higher, abnormal levels of methylation. However, the mechanism by which this change is involved in a cell’s transformation from normal to malignant is unclear. DNA methylation may play different roles in different types of cancer.

The nucleosomes around which DNA is wrapped are composed of eight histone proteins that have protruding lysine tails. This DNA–nucleosome complex is known as “chromatin.” Histones can be modified in several ways. Addition of acetyl molecules to the lysine tails causes the nucleosomes to move farther apart, unwinding the DNA and making it accessible for transcription. This active DNA is also marked by methylation of a specific lysine (K4) on a particular histone (H3). When acetyl molecules are not attached to the histones, DNA is tightly wound around them and inaccessible for translation. Inactive DNA is marked by methylation of a different lysine (K9) on the H3 histone. The inactivated X chromosome in female mammals contains this type of epigenetic modification. As a result, both males and females have the same amounts of X-chromosome gene products.

Exploring epigenetics provides students with a tangible example of environmental influences on genes. Thus, it can help them envision the factors that regulate gene expression. The Genetic Science Learning Center (GSLC) at the University of Utah has developed a free supplemental curriculum module that introduces epigenetics to high school and undergraduate students. Available on the Learn.Genetics (http://learn.genetics.utah.edu) website, this collection of interactive online and paper-based activities provides a basic understanding of the epigenome and how it instructs DNA. Because the materials are designed for an introductory level, they focus on two epigenetic modifications whose roles can be clearly explained: DNA methylation and histone acetylation. In addition, to reduce vocabulary load and potential confusion between the words “nucleosome” and “nucleus,” the materials simplify nucleosomes to histone proteins. The module also discusses our emerging understanding of the connections between the epigenome, environment, and behavior as well as discoveries about epigenetic inheritance. Support materials for educators include learning objectives and sample assessment questions for each activity, suggestions from the teachers who were involved in developing the module about ways to tie epigenetics to existing curricula, and a videotaped talk given by an epigenetics researcher during the module’s development process. The epigenetics module has been field tested in high school classrooms. The results showed that students who used the GSLC unit had a significantly higher knowledge gain than those in a control group.

The module’s activities can be used individually to supplement your genetics unit, or together as an epigenetics “mini unit” for a more detailed look at the epigenome. Here, we provide a brief overview of each activity, organized in a suggested framework for how the activities might be grouped together to provide basic and more advanced explorations of epigenetics (Table 1). Further, we describe the module’s alignment to AFramework for K–12 Science Education: Practices, Crosscutting Concepts, and Core Ideas (National Research Council [NRC], 2011) and the Next Generation Science Standards (NGSS) (NGSS Lead States, 2013), along with research findings on teachers’ implementation of the module and student learning.

Table 1.

Epigenetics module activities to use in addressing specific topics, suggested activity sequence, and connections to other genetics concepts.

To cover this topic:Do these activities in sequence:Connections to Genetics Concepts
How Does the Epigenome Work? 
  1. The Epigenome at a Glance: http://learn.genetics.utah.edu/content/epigenetics/intro

  2. Gene Control: http://learn.genetics.utah.edu/content/epigenetics/control

  3. DNA and Histone Model: http://learn.genetics.utah.edu/content/epigenetics/teacher

 
Factors controlling gene expression
Transcription and translation
Chromosome structure 
Epigenetics & the Environment 
  1. The Epigenetics of Identical Twins: http://learn.genetics.utah.edu/content/epigenetics/twins

  2. Lick Your Rats: http://learn.genetics.utah.edu/content/epigenetics/rats

  3. Your Environment, Your Epigenome: http://learn.genetics.utah.edu/content/epigenetics/teacher

 
Gene–environment interactions 
Advanced Topics in Epigenetics See article for a description of activities covering epigenetics as a “cellular memory,” epigenetic inheritance, nutrition and the epigenome, and the potential connection between epigenetics, behavior, and psychiatric disorders Developmental biology, cell biology, DNA replication, gene–environment interactions 
To cover this topic:Do these activities in sequence:Connections to Genetics Concepts
How Does the Epigenome Work? 
  1. The Epigenome at a Glance: http://learn.genetics.utah.edu/content/epigenetics/intro

  2. Gene Control: http://learn.genetics.utah.edu/content/epigenetics/control

  3. DNA and Histone Model: http://learn.genetics.utah.edu/content/epigenetics/teacher

 
Factors controlling gene expression
Transcription and translation
Chromosome structure 
Epigenetics & the Environment 
  1. The Epigenetics of Identical Twins: http://learn.genetics.utah.edu/content/epigenetics/twins

  2. Lick Your Rats: http://learn.genetics.utah.edu/content/epigenetics/rats

  3. Your Environment, Your Epigenome: http://learn.genetics.utah.edu/content/epigenetics/teacher

 
Gene–environment interactions 
Advanced Topics in Epigenetics See article for a description of activities covering epigenetics as a “cellular memory,” epigenetic inheritance, nutrition and the epigenome, and the potential connection between epigenetics, behavior, and psychiatric disorders Developmental biology, cell biology, DNA replication, gene–environment interactions 

The Epigenetics Module in the Classroom

Teaching the Basics Part 1: “How Does the Epigenome Work?”

Begin an exploration of epigenetics by showing students a brief (<2 minutes) introductory animated movie, The Epigenome at a Glance (http://learn.genetics.utah.edu/content/epigenetics/intro/). The movie demonstrates the basic mechanisms by which the epigenome operates in response to external signals. Discuss with students how gene expression depends on molecular interactions that take place in the nucleus as well as on a gene’s accessibility. Some molecules allow the chemical interactions that initiate transcription to take place, while other molecules block those interactions from happening.

Next, have your students explore the online “Gene Control” interactive activity (http://learn.genetics.utah.edu/content/epigenetics/control/), where they take on the role of a cellular signal that influences epigenetic tags and gene expression. By manipulating a control dial, students change the signal level, which, in turn, alters the epigenetic tags, the transcription level of mRNA, and the amount of GFP (green fluorescent protein) produced (for details, see Figure 1). Optional labels (turned on and off using the button in the upper right corner of the animation) introduce vocabulary. Clicking on information icons provides details about the molecules involved. Optional sound draws another connection between the level of chromatin compaction and gene expression; the sound button in the upper right corner of the animation is light green when the sound is on and dark green when it is off. Additional content on the page addresses the research on which the activity is based and the link between gene control and cancer. Discuss with students what they notice about the relationship between the amounts of mRNA and GFP protein produced as they manipulate the cellular signal. This will help reinforce the linkage between genes, mRNA transcripts, and protein products. When a gene is accessible and “active,” more mRNA transcripts are produced, resulting in greater protein production.

Figure 1.

Screen shots from the “Gene Control” interactive animation depicting the effect of changes in the level of a cellular signal on types of epigenetic tags in the chromatin complex and, thus, on levels of mRNA transcript and green fluorescent protein (GFP). (A) At a high signal level, the histone proteins (blue) have acetyl epigenetic tags (red dots) on their protruding tails, which results in loose coiling of the chromatin complex. The gene coding for GFP is available for transcription, and high levels of mRNA transcript are produced from it. The large amounts of GFP that are translated from the mRNA cause the cell to glow a bright green. (B) At a moderate signal level, the histone proteins have some acetyl epigenetic tags and the DNA (yellow) has some methyl tags (green dots). The DNA is more tightly wound around the histones, and less mRNA and GFP are produced. Therefore, the cell glows less brightly. (C) At a low signal level, the DNA has many methyl tags and the histones do not have acetyl tags. The chromatin is tightly compacted, and the DNA has little availability for transcription. Thus, very little mRNA transcript is made, little GFP is produced, and the cell is not green.

Figure 1.

Screen shots from the “Gene Control” interactive animation depicting the effect of changes in the level of a cellular signal on types of epigenetic tags in the chromatin complex and, thus, on levels of mRNA transcript and green fluorescent protein (GFP). (A) At a high signal level, the histone proteins (blue) have acetyl epigenetic tags (red dots) on their protruding tails, which results in loose coiling of the chromatin complex. The gene coding for GFP is available for transcription, and high levels of mRNA transcript are produced from it. The large amounts of GFP that are translated from the mRNA cause the cell to glow a bright green. (B) At a moderate signal level, the histone proteins have some acetyl epigenetic tags and the DNA (yellow) has some methyl tags (green dots). The DNA is more tightly wound around the histones, and less mRNA and GFP are produced. Therefore, the cell glows less brightly. (C) At a low signal level, the DNA has many methyl tags and the histones do not have acetyl tags. The chromatin is tightly compacted, and the DNA has little availability for transcription. Thus, very little mRNA transcript is made, little GFP is produced, and the cell is not green.

Complementing the online “Gene Control” activity is the paper- based “DNA and Histone Model” activity (download this copy-and-cut paper model from http://learn.genetics.utah.edu/content/epigenetics/teacher). You can use the models for many classes if you laminate the pages before you cut out the pieces. An additional modification is to add a stick-on hook-and-pile dot (i.e., Velcro) to the ends of the laminated histone molecules so that they can be formed into cylinders without using tape. A short video provides an activity tutorial for teachers. Have your students construct and manipulate this model to provide a tactile representation of how methyl and acetyl tags control access by the transcription machinery to DNA (Figure 2). This activity nicely demonstrates genes in the active and inactive states. As your students work with the models, walk around the room and ask them to demonstrate a gene that is turned “on” and one that is turned “off” to check for understanding of these concepts.

Figure 2.

The “DNA and Histone Model” paper-based activity. (A) When there are no acetyl tags on the histones, the chromatin is tightly coiled. Methyl tags on the DNA make it inaccessible to the gene-reading machinery. (B) When acetyl tags attach to the histone tails and methyl tags are removed from the DNA, the DNA is loosely wound around the histones. The gene-reading machinery can access the DNA and transcribe the exposed gene(s).

Figure 2.

The “DNA and Histone Model” paper-based activity. (A) When there are no acetyl tags on the histones, the chromatin is tightly coiled. Methyl tags on the DNA make it inaccessible to the gene-reading machinery. (B) When acetyl tags attach to the histone tails and methyl tags are removed from the DNA, the DNA is loosely wound around the histones. The gene-reading machinery can access the DNA and transcribe the exposed gene(s).

Together, these activities highlight the plasticity of DNA packaging and the role of epigenetic tags in gene expression. Individually, they can help students envision factors that influence gene expression and conceptualize why and how some genes are expressed while others are not.

Teaching the Basics Part 2: “Epigenetics & the Environment”

If you have time to delve a little deeper into epigenetics, engage your students in exploring environmental influences on the epigenome. First, follow a set of identical twins to see how their epigenomes come to differ over time in an introductory movie (<5 minutes), The Epigenetics of Identical Twins (http://learn.genetics.utah.edu/content/epigenetics/twins/). As the twins are exposed to differing environmental factors, their epigenomes become increasingly different. The movie highlights how throughout our lifetime, external factors such as diet, exercise, toxin exposure, and stress can directly shape the expression of our genes through epigenetics. Ask students to identify the environmental factors portrayed in the movie (stress, toxins, diet, and exercise) and what they know about how each affects overall health. Remind them that these impacts on health may ultimately be due to epigenetics and gene expression. Additional content on this page highlights how researchers use studies of identical and fraternal twins to help identify the relative effects of genes and environment on complex traits and diseases, which are both due to the interaction of multiple factors.

For an interactive experience with how cues from the environment can affect the epigenome, have students try their hand at nurturing a rat pup in the “Lick Your Rats” online activity (http://learn.genetics.utah.edu/content/epigenetics/rats/). If you are projecting the animation in your classroom, invite several students to each take a turn with the computer mouse, clicking the mother to lick the pup; differing click speeds simulate different levels of nurturing. Students will discover that the level of a mother’s nurturing behavior alters epigenetic tags associated with a particular stress-response gene in the pup’s brain cells. Her ability to nurture will have a long-term epigenetic consequence for the pup’s stress response, even as an adult. A simplified description of this mechanism is provided. However, your degree of focus on the details will depend on the level of students in your class. Engage your students in discussing environments in which anxious or relaxed behavior might be an advantage. Additional content on this page summarizes research studies showing that the epigenetic patterns for behavioral differences due to nurturing level in rats can be reversed.

Finally, after exploring how different cues from the environment may have epigenetic consequences, students can reflect on the factors in their own environment that might be leaving an epigenetic signature by completing the print-based “Your Environment, Your Epigenome” checklist (http://learn.genetics.utah.edu/content/epigenetics/teacher). Suggestions for discussion points are provided.

The epigenome is complex and shaped by countless cellular signals, including many from the environment. While there is still much to be learned, these activities highlight several recently uncovered links between environmental factors and the epigenome. They can be used to introduce students to the dynamic interaction between genes and the environment.

Advanced Topics in Epigenetics

Challenge students to think deeply and apply their knowledge of basic inheritance, genetics, and epigenetics by exploring the graphically rich “Learn More” web pages contained in the module.

“The Epigenome Learns from its Experiences” (http://learn.genetics.utah.edu/content/epigenetics/epi_learns/) highlights how epigenetic tags may act as a kind of “cellular memory.” Epigenetic tags can be copied and passed to daughter cells, essentially creating a record of the cell’s past. This content bridges genetics and developmental biology, as epigenetics explains how cells with an identical DNA sequence differentiate on the basis of their local environment and history.

In some instances, epigenetic marks can be passed from parent to offspring. “Epigenetics and Inheritance” (http://learn.genetics.utah.edu/content/epigenetics/inheritance/) considers the ways in which epigenetic tags can transfer across generations, bypassing traditional notions of genetic inheritance. The “Examples of Epigenetic Inheritance” slideshow on this page can be projected in class, providing an opportunity to discuss cases in plants and animals. Follow the link on the page to learn more about genomic imprinting and the role that epigenetics plays in silencing genes from one parent in offspring.

“Nutrition and the Epigenome” (http://learn.genetics.utah.edu/content/epigenetics/nutrition/) explores how an individual’s diet, along with their parents’ and even grandparents’ diet, can affect gene expression and health.

Finally, “Epigenetics and the Human Brain” (http://learn.genetics.utah.edu/content/epigenetics/brain/) examines potential connections between epigenetics, behaviors, and psychiatric disorders, because epigenetic tags are active and influential in brain cells.

The content on these “Learn More” web pages is appropriate for students who can move beyond the “what” and “how” of epigenetics to consider the greater implications of gene–environment interactions. Citations for the original research articles on which the module content is based are included at the bottom of the pages to facilitate further exploration by interested or advanced students.

Connections to the Framework for K–12 Science Education and the Next Generation Science Standards

The module aligns with science practices, crosscutting concepts, and life-sciences disciplinary core ideas outlined in the Framework for K–12 Science Education (NRC, 2011) and the NGSS (NGSS Lead States, 2013). Science practices include developing and using models (P2) and constructing explanations (P6). The module emphasizes and integrates the crosscutting concepts of cause and effect (CC2) and structure and function (CC6). Finally, the disciplinary core ideas found in the module include cellular differentiation (LS1.B), how organisms respond to signals from the environment (LS1.D), the regulation of gene expression (LS3.A), and the influence of environmental factors on trait expression (LS3.B) (NRC, 2011). Ties to the Framework and NGSS are evident throughout the activities.

Study Findings on the Module’s Effectiveness & Implementation

The findings from recent studies showed that these epigenetics materials foster student learning and promote technology integration in the science classroom. In a randomized controlled study, 145 high school biology students were randomly assigned to treatment or control lessons. The treatment lessons used activities from the GSLC’s epigenetics module, and the control lessons used NOVA “scienceNOW” materials, the only other curriculum materials for high school students on epigenetics that we were aware of at that time.

Activities were selected from the GSLC module so that both the treatment and control lessons addressed the same concepts and were the same length. Both sets of lessons included multimedia materials and student manipulation of a physical model. Several of the GSLC multimedia materials were interactive, whereas the NOVA materials were not. “The Epigenome at a Glance,” “Gene Control,” “DNA and Histone Model,” “The Epigenetics of Identical Twins,” “Lick Your Rats,” and “Your Environment, Your Epigenome” were used in the treatment lessons. The control lessons included a movie titled Epigenetics, an audio slide show titled “A Tale of Two Mice”; a brainstorming activity in which students created analogies and similes (“Analogies and Similes”); and a hands-on model. Students who experienced the GSLC epigenetics lessons showed significantly higher (P < 0.05) knowledge gains than those in the control group (D. Drits-Esser et al., unpublished data).

A large-scale survey research study of >1000 educators asked how they implemented the epigenetics module in their science classroom. The findings showed that the organization and structure of the technology-based and complementary print-based materials facilitated teachers’ integration of technology in their science lessons (D. Drits-Esser et al., unpublished data). The results also suggested that the flexibility of the curriculum materials allows teachers to modify and adapt the materials to meet their individual needs. The researchers concluded that because the GSLC’s curriculum development process utilizes research-based approaches to curriculum design and engages teachers early in the process, the resulting curricula are accessible and relevant to teachers, address science standards, and are easy to integrate in the classroom (D. Drits-Esser et al., unpublished data).

Summary & Conclusion

Students often struggle to make connections between the simple model of single-gene Mendelian inheritance and the vastly more common but complicated patterns of inheritance that arise from interactions among multiple genes and the environment. The GSLC’s epigenetics module introduces students to the context dependence of gene expression and how external cues and signals can influence expression. Connecting gene expression to factors in students’ own environment through online and print-based components can add excitement, interest, and relevance to any biology classroom.

References

References
Egger, G., Liang, G., Aparacio, A. & Jones, P.A. (2004). Epigenetics in human disease and prospects for epigenetic therapy. Nature, 429, 457–463.
National Research Council. (2011). A Framework for K–12 Science Education: Practices, Crosscutting Concepts, and Core Ideas. Washington, DC: National Academies Press.
NGSS Lead States. (2013). Next Generation Science Standards: For States, By States. Washington, DC: National Academies Press.
PBS Online. (2007a). A tale of two mice. NOVA scienceNow. http://www.pbs.org/wgbh/nova/body/epigenetic-mice.html.
PBS Online. (2007b). Epigenetics. NOVA scienceNow. http://video.pbs.org/video/1525107473/.
PBS Online. (2007c). Epigenetics [teacher guide]. NOVA scienceNow. http://www.pbs.org/wgbh/nova/education/activities/pdf/3411_02_nsn.pdf.
PBS Online. (2007d). NOVA scienceNOW: Epigenetics viewing ideas. http://www.pbs.org/wgbh/nova/education/viewing/3411_02_nsn.html.
Simmons, D. (2008). Epigenetic influences and disease. Nature Education, 1, 6. http://www.nature.com/scitable/topicpage/epigenetic-influences-and-disease-895 [provides a freely available, nontechnical summary of the Egger article and others].
Suvà, M.L., Riggi, N. & Bernstein, B.E. (2013). Epigenetic reprogramming in cancer. Science, 339, 1567–1570.