Lecture 13 Reading

Question 1

The basics of epigenetics

Answer 1

Epigenetics: the study of changes in organisms caused by modification of gene expression rather than alteration of the genetic code itself

Epigenetic marks ○ Can be on the DNA or the histone ○ Can inhibit or activate gene transcription by condensing or loosening the chromatin ● Epigenetic modifications are made by various enzymes ○ “Writers” → create the mark on the chromatin ■ Ex: histone acetyltransferase add an acetyl group to a histone protein ○ “Erasers” → remove the mark in the chromatin ■ Ex: histone deacetylase removes the acetyl group ○ “Readers” → other proteins that bind to specific epigenetic tags and can loosen or condense the chromatin by recruiting other regulatory proteins that stimulate or repress gene transcription

Question 2

Thypes of epigenetic marks

Answer 2

Can be on the DNA or the histone

-Can inhibit or activate gene transcription by condensing or loosening the chromatin

Epigenetic modifications are made by various enzymes ○ “Writers” → create the mark on the chromatin

• Ex: histone acetyltransferase add an acetyl group to a histone protein ○ “Erasers” → remove the mark in the chromatin
• Ex: histone deacetylase removes the acetyl group ○ “Readers” → other proteins that bind to specific epigenetic tags and can loosen or condense the chromatin by recruiting other regulatory proteins that stimulate or repress gene transcription

Question 3

Epigenetics and addiction

What does cocaine do to mice? In what region of the brain?

What happens wheen there is no cocaine present? And when there is?

What does chronic exposure do?

Answer 3

Studies of mice have shown that chronic cocaine exposure shifts the balance of epigenetic marks on genes in the brain’s reward center (particularly in the nucleus accumbens)

-This shift makes the animal more sensitive to the drug’s effects and more prone to becoming addicted

When no cocaine is present, methyl marks predominate, keeping the affected chromatin tightly wound so that transcription cannot occur

When cocaine is present, acetyl groups predominate and the chromatin becomes loose so transcription can occur

-This allows proteins that are involved in the pleasurable response to the drug to be produced

The initial exposure to cocaine elevates the activity of many genes, but activity will eventually return to baseline

Chronic exposure can have more complex effects

• It makes some genes less sensitive to the drug
• It can boost the activity of other genes even higher than before

These genes can remain overactive for a long time (a month or more) even after drug use stops

Question 4

Epigenetics and behavior

What happens when you subject mice to social defeat?

What does depression do?

Answer 4

Subjecting mice to social defeat can make them become depressed

Depression may shut down genes important for activating the part of the brain that allows an animal to feel good

• Observed epigenetic modifications in 2,000 genes in the brain’s reward center
• For 1,2000 of these genes, they measured an increase in a form of histone methylation that represses gene activity

Not all mice are susceptible to depression

• Many of the stress-induced epigenetic changes observed in mice who get depressed are not seen in resilient mice
• These findings suggest that this alternative pattern of modification is protective and that resilience is more than just an absence of vulnerability, it involves an active epigenetic program that can be called on to combat the effects of chronic stress

Question 5

How does epigenetics affect maternal behavior?

How does attentive mothering affect methylation in pup brains?

Answer 5

Epigenetics can influence maternal behavior and this effect can be passed from one generation to the next by acting on the pup’s brain alone, without altering germ cells

When pups are born, genes involved in regulating the rodents’ stress response are decorated with inhibitory methyl marks which enhance sensitivity to stress

• Pup receives attentive mothering → methyl marks on pup’s genes are removed → pup grows up to be an attentive, relaxed mother
• Pup receives inattentive mothering → methyl marks are added → pup grows up to be an anxious, inattentive mother

Question 6

Can we “cure” epigenetics?

How might we do this and why would we want to?

Answer 6

Generate medicines that are able to selectively inhibit the forms of histone deacetylases that are enriched in areas of the brain most affected by psychiatric conditions

Identify novel proteins involved in epigenetic modification in the brain

Determine which genes are the subjects of epigenetic modification in depression or addiction

Question 7

Heritability of epigenetics

Answer 7

Generate medicines that are able to selectively inhibit the forms of histone deacetylases that are enriched in areas of the brain most affected by psychiatric conditions

• Identify novel proteins involved in epigenetic modification in the brain
• Determine which genes are the subjects of epigenetic modification in depression or addiction

Question 8

Do epigenetics only occur in fetal development?

Can they get passed intergenerationally?

How does diet change things?

Answer 8

Epigenetic changes were once believed to only occur during fetal development, but we now know this is not true

-They can occur later and can set off a cascade of cellular resulting in cancer, for example

Epigenetic changes can be passed from down from one generation to the next

Diet and chemical changes can cause epigenetic changes - and so can experience (behavioral epigenetics)