13. Gene Regulation in Eukaryotes

Define epigenetics, and provide examples illustrating your definition.

What are the differences and similarities among the three classes of monoallelic gene expression?

Describe the manner in which activators and repressors influence the rate of transcription initiation. How might chromatin structure be involved in such regulation?

Imprinting disorders do not involve changes in DNA sequence, but only the methylated state of the DNA. Does it seem likely that imprinting disorders could be treated by controlling the maternal environment in some way, perhaps by dietary changes?

Should fertility clinics be required by law to disclose that some assisted reproductive technologies (ARTs) can result in epigenetic diseases? How would you and your partner balance the risks of ART with the desire to have a child?

How can the role of epigenetics in cancer be reconciled with the idea that cancer is caused by the accumulation of genetic mutations in tumor-suppressor genes and proto-oncogenes?

How are mutations in histone acetylation (HAT) genes linked to cancer?

A developmental disorder in humans called spina bifida is a neural tube defect linked to a maternal diet low in folate during pregnancy.

Should researchers be looking for mutant alleles of genes that control formation and differentiation of the neural tube?

A developmental disorder in humans called spina bifida is a neural tube defect linked to a maternal diet low in folate during pregnancy.

Does this exclude genetic mutations as a cause of this condition?

A developmental disorder in humans called spina bifida is a neural tube defect linked to a maternal diet low in folate during pregnancy.

What does this suggest about the cause of spina bifida?

Trace the relationship between the methylation status of the glucocorticoid receptor gene and the behavioral response to stress.

Because the degree of DNA methylation appears to be a relatively reliable genetic marker for some forms of cancer, researchers have explored the possibility of altering DNA methylation as a form of cancer therapy. Initial studies indicate that while hypomethylation suppresses the formation of some tumors, other tumors thrive. Why would one expect different cancers to respond differently to either hypomethylation or hypermethylation therapies?

Prader–Willi syndrome (PWS) is a genetic disorder with a clinical profile of obesity, intellectual disability, and short stature. It can be caused in several ways. Most common is a deletion on the paternal copy of chromosome 15, but it can also be caused by an epigenetic imprinting disorder and uniparental disomy, an event in which the affected child receives two copies of the maternal chromosome 15. A child with PWS comes to your clinic for a diagnosis of the molecular basis for this condition. The gel below shows the results of testing with short tandem repeats (STRs) from the region of chromosome 15 associated with the disorder.

Based on your interpretation of the data, what is the cause of PWS in this case? Explain your reasoning. 

Prader–Willi syndrome (PWS) is a genetic disorder with a clinical profile of obesity, intellectual disability, and short stature. It can be caused in several ways. Most common is a deletion on the paternal copy of chromosome 15, but it can also be caused by an epigenetic imprinting disorder and uniparental disomy, an event in which the affected child receives two copies of the maternal chromosome 15. A child with PWS comes to your clinic for a diagnosis of the molecular basis for this condition. The gel below shows the results of testing with short tandem repeats (STRs) from the region of chromosome 15 associated with the disorder.

Is this case caused by a deletion in the paternal copy of chromosome 15? Explain.

From the following table, draw up a list of histone H3 modifications associated with gene activation. Then draw up a list of H3 modifications associated with repression.

If not, how can you reconcile these differences?