Lecture 9: Epigenetics

Question 1

epigenetic trait

Answer 1

stably heritable phenotype resulting from changes in a chromosome without alterations in DNA sequence

Question 2

HATs vs HDACs

Answer 2

• histone acetylation transferases (gene activation)

- histone deacetylases (gene suppression)

Question 3

How do HATs work

Answer 3

HATs add positive acetyl group to histone tails which neutralizes the lysine in the histone tails and disrupts the interaction of the DNA with the histone thus exposing it

Question 4

Valproic acid

Answer 4

used to treat BPD, epilepsy, migraines

• is an HDAC inhibitor (more gene activation)
• can cause developmental abnormalities (7 fold chance of ASD in offspring of using mothers)
• used as ASD model sometimes

Question 5

DNA methylation most frequently occurs on

Answer 5

cytosine dinucleotide sequences (CpG) sites which are often found in regulatory regions including the promoter

Question 6

main effects of methylation

Answer 6

• Blocking (access to DNA is impaired)
• Docking (binding of other factors is permitted like other methyl binding proteins which then recruit HDACs making promoter of gene inaccessible)

Question 7

MeCP2

Answer 7

methyl CpG binding protein 2

- mutations linked to Rett syndrome

Question 8

Are methylation patterns heritable?

Answer 8

Via mitotic cell division, yes. Mechanism by which differentiated cells remain differentiated.
- patterns are erased early in reproduction (gamete production)

Question 9

MicroRNA as gene silencing

Answer 9

miRNAs base pair with complementary mRNA

• cleavage, shorterned polyA tail
• stops ribosome access (no protein)

Question 10

prenatal maternal immune activation

Answer 10

• associated with SZ risk in children and changes in DNA methylation in mice

Question 11

What affects DNA methylation in offspring

Answer 11

prenatal nutrition, prenatal stress, and cannabinoid use

Question 12

Agouti gene

Answer 12

In mice, gene causes obesity and high cancer risk. Silencing of the gene via DNA methylation can rescue the normal phenotype. Methyl donor foods.

Question 13

methyl donor foods

Answer 13

folic acid, vit B12, choline, and betaine

Question 14

Variations in maternal care in mice

Answer 14

licking and grooming (LG) behaviours vary between mothers and are associated with different offspring phenotypes

high LG
- modest stress response, low anxiety, high Glucocorticoid receptor (GR) gene expression

low LG
- strong stress response, high anxiety, low GR gene expression

Question 15

Landmark study on childhood abuse and GR genes

Answer 15

study found reduced GR and increased methylation in abused children.
- those who endured abuse and later completed suicide had increased methylation of the GR gene and decreased GR expression in the hippocampus

Question 16

NR3C1, OXTR, SLC6A4

Answer 16

gene for GR, oxytocin receptor, serotonin transporter

Question 17

Epigenetics in twins

Answer 17

as MZ twins age, their methylation patterns and histone acetylation patterns become increasingly different
- may be the reason for low concordance rate scores

Question 18

Transgenerational epigenetics

Answer 18

In mice, isolating the first generation showed effects in behavioural tests in later generations. In humans, food supply in grandparents linked to mortality and health in grandchildren (less food for gma = higher rates of mortality and obesity in grand kids)

Question 19

Criticisms of Transgenerational epigenetics

Answer 19

• weak results found in humans studies
• no suggestion of mechanism
• alternative explanations not considered (maybe the F0 mothers differ in maternal care which cause behavioural changes in offspring) behavioural transmission