NOVA scienceNOW: Epigenetics

Student Handout

Epigenetics

Epigenetics is a field of research that investigates heritable information carried in the cell that is not directly coded by DNA. The prefix epi, which comes from both Latin and Greek, means "above" or "outside." The term epigenetics refers to mechanisms controlling gene expression that are independent of the DNA sequence itself.

Methyl groups are one kind of chemical known to have an epigenetic effect. Methyl groups occur naturally, and the body obtains them through food and as natural products of metabolism. They enable the nucleus's very tightly wound chromatin to uncoil. Since they originate outside the DNA, methyl groups are considered epigenetic factors. Today, you will build a model of chromatin and explore how chromatin can be chemically influenced by factors originating from "outside" the DNA.

Procedure

1. Build a model of chromatin. Gather the materials you need to make a model similar to the one your teacher demonstrated. Mark and assemble the three tubes as follows:

   1. Make the first "DNA" tube: Using a ballpoint pen, mark the length of the tube using combinations of the letters A, C, T, G. The letters should be large and in random order. You can repeat letters, and two of the same letter can be next to each other. These letters represent the amino acids of the nucleotides (A for Adenine, C for Cytosine, T for Thymine, and G for Guanine).

   2. Make the second "DNA" tube: Lay a second length of tubing alongside the first tube. Where you've written an A on the first tube, mark a T on the second; where there's a T on the first, write an A on the second. Similarly, where you've written a C on the first, mark a G on the second; where there's a G on the first, mark a C on the second.

   3. Make the "histone" tube: Using a colored marker, put dots or stripes along the length of the third tube.

   4. Hold the ends of the three tubes together, keeping them as parallel as possible (i.e., no twists, overlaps, or kinks). It does not matter which tube is next to which. Wrap tape around the ends, securing the tubes together. Repeat with the other end of the tubes. You should end up with a single 24-inch unit made up of three strands.

2. Twist the tubes. With one person holding each end of the triple bundle, begin twisting it into a spiral. When it begins to form knots, continue to twist slowly while pulling gently outward. Maintain tension so that the first spiral of knots forms into a secondary spiral of knots.

3. Show how epigenetic factors control the behavior of chromatin. Use your model to show how chromatin uncoils to reveal the sequence of the nucleotides so they can be "read" by enzymes and then transcribed by messenger RNA.

   1. Select a zone about six inches long near the middle of the twisted tubes. Mark this zone by attaching a binder clip to the "histone" tube at each end of the zone. The clips represent chemicals called methyl groups that are able to attach to the histone complex.

   2. Have a third person from your group work to carefully uncoil the three tubes in the six-inch zone marked off by the clips.

   3. Once this zone is uncoiled, read the sequence of base pair letters on the DNA tubes. This models the way that enzymes would "read" DNA base pairs to transcribe messenger RNA.

   4. After reading the base pair sequence, carefully recoil the three tubes and remove the clips.

Questions
Write your answers on a separate sheet of paper.

1. Why can it be difficult for enzymes to "read" DNA base pairs in a coiled nucleosome?

2. 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.

3. How are methyl groups examples of an epigenetic factor?

4. What would happen if methyl groups stayed attached to the nucleosome forever and kept it continuously open?

5. List some ways that a nucleosome stuck in "continuous reading" mode might become unstuck.

6. List some strengths and weaknesses of this activity's model of the DNA–chromatin complex.

7. 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?