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Transcript
Framework for Teachable Unit
Topic: EPIGENETICS
Group Members’ Names: Alex, Ann, Michael, Rhishi, Tish, Yaldez, Vangelis, Jim
Learning Goal:
The aim of this unit is to help students understand the mechanisms of epigenetics and the role of epigenetics in organism health and
development
Learning Objectives:
The students will be able to:
1. Model histone – DNA interactions
2. Compare and contrast the impact of acetylation and methylation on gene expression
3. Evaluate an experiment that demonstrates epigenetic silencing
4. Discuss consequences of epigenetics on human health
Summative Assessments (describe how you would assess your objectives and paste in any summative assessments you have
created):
Drugs aimed at histone modifications are called histone deacetylase (HDAC) inhibitors. HDACs are enzymes that remove the acetyl
groups from DNA, which condenses chromatin and stops transcription. Blocking this process with HDAC inhibitors turns on gene
expression. The most common HDAC inhibitors include phenylbutyric acid, SAHA, depsipeptide, and valproic acid (Egger et al.,
2004).
A sick patient is found to have unusual patterns of histone acetylation on a gene X that causes the transformation of haematopoietic
cells into leukaemia stem cells.
Treating with HDAC inhibitors targeted at gene X would have which effect(s)? Mark all that are true.
_ increase in the gene expression of gene X
_ no change in gene expression of gene X
_ increase in the number of haematopoietic cells
_ decrease in the number of growing leukaemia stem cells
_ decrease in the affinity of histone tails for other nucleosomes
_ increase in the recruitment of gene silencing proteins to the histone tail
If a patient with cancer is found to have unusual patterns of methylation, then treating with HDAC inhibitors would have which
effect(s)? Mark all that are true.
_ decrease in the gene expression of gene X
_ no change in gene expression of gene X
_ increase in the number of haematopoietic cells
_ decrease in the number of growing leukaemia stem cells
_ decrease in the affinity of histone tails for other nucleosomes
_ increase in the recruitment of gene silencing proteins to the histone tail
This is the knowledge that the above question is testing:
Acetylation increases transcription by loosening the tail by:
1) adding (+) charge to the histone tail which reduces affinity for DNA (DNA loosens)
2) reduces affinity for other nucleosomes, reducing tightness of the second order structure
Methylation
1) No change in charge but methylation recruits silencing or repressive proteins to the site
Formative Assessments (activities/instruction you designed to teach the learner; please describe your instructional methods
referring your PowerPoint presentation so that others could give this presentation at their own institution.)
An experimental technique called chromatin immunoprecipitation is used to assess DNA protein interactions.
The protein complex bound DNA (Example: DNA and histones in nucleosomes) can be detected by amplifying the target DNA by
PCR. Researchers used this technique to study the promoter of an organ specific gene - GATA4 which is exclusively expressed in
heart and no other cell type. The amplification product from the experiment is measured and is proportional to the strength of DNAhistone interaction (Figure 1).
Which bar represents the heart and which the brain?
In mutant cells, the GATA4 gene expression was seen to be abolished in heart cells. Successive experiments annotated the function
of the mutant genes to be a histone deacetylase that removed the acetyl group from the histone proteins.
In order to study the changes in promoter of GATA4, scientists repeated the chromatin immunoprecipitation experiment. Which of
the following graphs describes the outcome of the experiment?