What causes the physical appearance and health status of identical twins to diverge with age? In this lesson, students learn that the environment can alter the way our genes are expressed, making even identical twins different. After watching a PBS video, A Tale of Two Mice, and reviewing data presented in the Environmental Health Perspectives article Maternal Genistein Alters Coat Color and Protects Avy Mouse Offspring from Obesity by Modifying the Fetal Epigenome, students learn about epigenetics and its role in regulating gene expression.
Author Dana Haine, MS University of North Carolina at Chapel Hill Superfund Research Program
Reviewers Dana Dolinoy, PhD University of Michigan
Rebecca Fry, PhD University of North Carolina at Chapel Hill Superfund Research Program
Banalata Sen, PhD, Audrey Pinto, PhD, Susan Booker, Dorothy Ritter Environmental Health Perspectives
The funding for development of this lesson was provided by the National Institute of Environmental Health Sciences and the UNC Superfund Program.
By the end of this lesson students should be able to: define the term “epigenetics” describe DNA methylation as a mechanism for inhibiting gene transcription describe how gene expression can vary among genetically identical offspring
Bio.3 Explain how traits are determined by the structure and function of DNA.
Bio.3.2 Explain how the environment can influence the expression of genetic traits. Bio.4 Understand how biological molecules are essential to the survival of living organisms. Bio.4.1 Summarize the relationship among DNA, proteins and amino acids in carrying out the work of cells and how this is similar in all organisms. Bio.3 Understand the application of DNA technology.
Bio.3.3 Interpret how DNA is used for comparison and identification of organisms.
Note to Teacher: This lesson is best conducted after students have learned about general DNA structure and function; transcription and translation; general regulation of gene expression.
Communication (note-taking, oral, written – including summarization) Comprehension (listening, reading) Critical thinking and response Graph reading Figures (reading legends)
45-60 minutes Depending on student proficiency level, this lesson can be completed as a homework assignment to encourage independent student work and/or to save class time.
Computer with Internet access and audio (sound) capabilities LCD Projector Accompanying Powerpoint slide library (optional) Student worksheet, one copy per student
Ensure students have a basic understanding of DNA structure and function prior to introducing the concept of epigenetics. Students should already be familiar with the following terminology: o Chromatin o Chromosome o Deoxyribonucleic acid (DNA) o Gene o Gene expression/regulation o Histone proteins o Nitrogenous base o Nucleoprotein
o Nucleotides o Phosphodiester bond o Promoter o Ribonucleic acid (RNA) o Transcription o Transcription factors o Translation
Review the Background Information, Procedure and Student Instructions for this activity. Additional resources are listed in the Resources section. Make copies of the Student Worksheet, one per student.
Deoxyribonucleic acid (DNA) is a large, complex molecule (macromolecule) that contains the genetic code or the information needed to direct the activities of a cell and for transmission of this information to the next generation. A single DNA strand is made up of building blocks called nucleotides that are connected together like a chain. Each DNA nucleotide is composed of a nitrogenous base—either adenosine (A), guanine (G), thymine (T), or cytosine (C)—a five-carbon deoxyribose sugar (S), and a phosphate group (P). A gene is a specific sequence of nucleotides within a DNA strand that provides the
DNA exists as a double-stranded polymer of nucleotides that forms a helix in which two DNA strands run anti-parallel to one another and interact via hydrogen bonds between the nitrogenous bases. The hydrogen bonds between the nitrogenous bases can be broken to allow the DNA strands to separate during
The histone proteins that hold DNA tightly wound inside each cell can also be modified by methylation or other modifications such as acetylation or phosphorylation. When too much or too little of a given histone modification occurs, it affects a gene’s expression and consequently its function, which causes unwanted alterations in the cell, potentially resulting in disease.
Epigenetic modifications can be maintained and inherited by daughter cells during mitosis and to a lesser extent during meiosis. Therefore, epigenetic modifications that occur in utero can be passed on to subsequent generations. Environmental factors such as exposure to heavy metals (arsenic, nickel) and cigarette smoke, and dietary factors such as vitamin and folate deficiencies have been linked to abnormal changes in epigenetic pathways, suggesting that an individual’s environment plays an important role in shaping their epigenome. Epigenetic changes have been observed in different stages of cancer progression, in the process of aging, and in other human diseases such as Alzheimer’s disease, diabetes and obesity.
In A Tale of Two Mice (pbs/wgbh/nova/genes/mice.html), the narrator discusses the difference in coat color between two genetically identical mice. The obese, yellow mouse has an unmethylated Agouti gene, which is constantly being expressed (when it normally should be “off ” or silenced), while her sister, the brown mouse, has a methylated Agouti gene that has permanently been turned “off ” and thus is not expressed. Although genetically identical in terms of the DNA sequences they’ve inherited from their mother and father (the mice are inbred), epigenetic modifications have led one mouse to be overweight and more susceptible to diabetes and cancer. This difference in gene expression between the genetically identical mice can be attributed to differential gene expression as a result of epigenetic modifications.
Figure 2: The addition of methyl groups to CpG islands common to promoters is one mechanism for suppressing (or silencing) gene transcription (Image: Fry, 2011).
Ask students to turn in their completed worksheets (Answer Key provided). Ask student to summarize, in their words, what they learned during this activity. Ask students to construct a concept map using critical vocabulary terms (see below) along with vocabulary terms from page 2 to demonstrate they understand the concept of epigenetics in the
Definitions for the terms below were obtained from the National Institute of Health, Genetics Home Reference Handbook ghr.nlm.nih/handbook/howgeneswork/epigenome
Epigenetics: refers to heritable changes in the regulation of the expression of gene activity without alteration of genetic structure.
DNA Wrap – Packaging Matters Student Worksheet Answer Key
Watch Chapter 1 of the video “A Tale of Two Mice,” and be prepared to discuss these questions as a class:
Step 2 The figure below shows the location of chromosomes within a cell and the composition (i., DNA and structural proteins) and three-dimensional structure of chromosomes. Individually, or with a partner, use your textbook if necessary, to:
Science Education Program
Step 3 Research suggests that the way DNA is “packaged” into chromatin plays an important role in genetic processes like DNA replication, recombination, repair, and transcription. This means that changes in gene expression (i., the yellow mouse versus the brown mouse in the video you saw) can occur without changes in the DNA structure itself (mutation).
Epigenetics is the study of other factors besides the DNA sequence that influence whether or not a gene is transcribed into mRNA and then translated (conversion of mRNA sequence into amino acids) into a protein. An individual’s environment, even in the womb, can influence these factors and permanently alter the expression of genes in the adult. Alterations in epigenetic mechanisms lead to development of diseases, such as some forms of cancer, including colorectal cancer and leukemia, neurodevelopmental disorders, obesity, and type 2 diabetes.
Your teacher provided you with an example of an epigenetic mechanism called DNA methylation that prevents a gene from being expressed (transcribed and translated into its protein product); this is also known as suppression of gene expression or gene silencing.
After learning about methylation and viewing Chapter 2 of “A Tale of Two Mice,” summarize in your own words how this epigenetic modification affects DNA structure and function.
Answers will vary, but should indicate student understanding that methylation suppresses transcription of a gene by preventing the gene from being accessed by enzymes such as RNA polymerase that are essential for transcription to occur.
Step 4 Below are the experimental results published in Figures 4 and 5 of the Environmental Health Perspectives article Maternal Genistein Alters Coat Color and Protects Avy Mouse Offspring from Obesity by Modifying the Fetal Epigenome.
In this study, pregnant mice were exposed to genistein, a component of soy, to determine if exposure to genistein influenced gene expression among genetically identical offspring.
Look at the experimental results above (Figures 4 and 5) and complete the table on the next page before answering the questions that follow:
DNA Wrap – Packaging Matters Student Worksheet Name:
Watch Chapter 1 of the video “A Tale of Two Mice,” and be prepared to discuss these questions as a class:
Step 2 The figure below shows the location of chromosomes within a cell and the composition (i., DNA and structural proteins) and three-dimensional structure of chromosomes. Individually, or with a partner, use your textbook if necessary, to:
WRAP– Science Education Program
Step 3 Research suggests that the way DNA is “packaged” into chromatin plays an important role in genetic processes like DNA replication, recombination, repair, and transcription. This means that changes in gene expression (i., the yellow mouse versus the brown mouse in the video you saw) can occur without changes in the DNA structure itself (mutation).
Epigenetics is the study of other factors besides the DNA sequence that influence whether or not a gene is transcribed into mRNA and then translated (conversion of mRNA sequence into amino acids) into a protein. An individual’s environment, even in the womb, can influence these factors and permanently alter the expression of genes in the adult. Alterations in epigenetic mechanisms lead to development of diseases, such as some forms of cancer, including colorectal cancer and leukemia, neurodevelopmental disorders, obesity, and type 2 diabetes.
Your teacher provided you with an example of an epigenetic mechanism called DNA methylation that prevents a gene from being expressed (transcribed and translated into its protein product); this is also known as suppression of gene expression or gene silencing.
After learning about methylation and viewing Chapter 2 of “A Tale of Two Mice,” summarize in your own words how this epigenetic modification affects DNA structure and function.
Step 4 Below are the experimental results published in Figures 4 and 5 of the Environmental Health Perspectives article Maternal Genistein Alters Coat Color and Protects Avy Mouse Offspring from Obesity by Modifying the Fetal Epigenome.
In this study, pregnant mice were exposed to genistein, a component of soy, to determine if exposure to genistein influenced gene expression among genetically identical offspring.
Look at the experimental results above (Figures 4 and 5) and complete the table on the next page before answering the questions that follow:
