epigenetic diseases

Question 1

epigenetics and cancer

Answer 1

• promoters of tumor suppressor genes like BRCA1 are often hypermethylated (checkpoints don’t work)
• changes in histone modifications also found

Question 2

Rett Syndrom (autism-like disease)

Answer 2

• MeCP2 (methyl cytosine binding protein 2) binds methylated Cs and is a reader of epigenetic modifications
• recruits additional enzymes that modify adjacent gene regions in way that represses expression and permanently shut off gene expression
• rett syndrome affects 1/15,000 (primarily girls) and is normal at birth but displays motor/mental/social/respiratory deficits after months or years
• caused by random spontaneous mutations in gene coding for MeCP2 which leads to its inactivation and loss of expression

Question 3

Cortisol and disease

Answer 3

• steroid hormone produced by adrenal gland in response to stress
• cortisol levels are elevated in most adults who suffered psychological damage as a child due to chronic stress
• has a negative feedback loop: cortisol shuts down expression of coritcotropin-releasing hormone (CRH) and adrenocorticotropic hormone (ACTH)
• too much cortisol = cushings disease
• too little cortisol = addison’s disease

Question 4

effects of good and bad mothering on rats (pup-swapping)

Answer 4

• raised by good mom = chilled out = low ACTH and cortisol, high serotonin
• serotonin stimulates and HAT which leads to reduced CpG island methylation of glucocorticoid receptor gene, leading to higher expression in the hippocampus
• cortisol binds GR leading to increased expression of anti-inflammatory proteins in the nucleus and cytosol
• well cared for pups also had increased acetylation of H3K9 and TF binding in GR promoter (more GR expressed = more functioning cortisol)

Question 5

epigenetics and depression

Answer 5

-SSRIs lead to increased serotonin almost immediately but take weeks to see improvement in symptoms
- in social defeat experiment, resilient mice had normal CRF levels and increased methylation at promoter for gene of CRF
- susceptible mice had high CRF levels and decreased methylation at promoter for gene for CRF

• CRF - corticotrophin releasing factor: normally methylated and silent

Question 6

Warrior gene

Answer 6

-Monoamine oxidase inhibitor A (MAO A) is enzyme that breaks down amines such as norepinephrine, serotonin, and dopamine and inhibits the effects of these hormones
- variants of the gene have been identified that have different numbers of a repeated sequence in the upstream region of the promoter
- fewer repeats leads to lower promoter activity in two different cell lines
- more repeats lead to more recruitment sites = higher promoter activity
- variants with lower MAO A activity = higher levels of NE, serotonin/dopamine = high levels of aggression