Cycle 11: Epigenetics

Question 1

What is epigenetics? What does it do?

Answer 1

“the study of changes in gene expression caused by mechanisms other than changes in underlying DNA sequence”

preprogrammed tags on top of DNA sequence

tags are METHYL group (CH3) and ACETYL groups

controls gene expression - dynamic (tags)

Question 2

What are histones?

Answer 2

proteins that DNA wraps around to stay condensed in nucleus (ex. spool)

coded for in genome - transcribed and translated - and has Ac tail

protein - made of AA - not nucleotides like DNA

Question 3

How do histones let DNA wrap around?

Answer 3

DNA is negatively charged from phosphate groups

overall positive charge in histones from positively charged AA - LYSINE (K)

Question 4

What is the difference between genome and epigenome?

Answer 4

genome - DNA sequence, unchanging

epigenome - tag sequence, dynamic based on life experiences controlling gene expression (not random)

Question 5

How does the epigenome of twin compare?

Answer 5

identical genome and epigenome at birth but very different epigenome with age

Question 6

Can you have methylation/acetylation mutations?

Answer 6

Yes!
normal DNA supposed to not be methylated but mutated is

normal DNA supposed to be acetylated but mutated is not

and vice versa

Question 7

What are DNMTs? What are TET?

Answer 7

DNMT: enzyme - DNA methyltransferase - adds methyl group to cytosine on DNA

TET - ten-eleven translocation enzyme does demethylation

Question 8

How is DNA methylated and demethylated?

Answer 8

this happens on cytosines that have guanine next to it (CpG region) on both strands

1. DNA double strand with no methyl groups
2. DNMT3A + DNMT3B guided by signal transduction to add methyl groups to specific cytosine
3. DNA replication causes parent strand to have methylation and new strand to not - hemimethlyated stands
4. DNMT1 maintains DNA methylation by adding methyl groups to new strands
5. TET - removes methyl groups from cytosine

Question 9

What the effect of methylation and demethylation on gene expression?

Answer 9

hypermethylation/methylation - inactivates transcription (gene expression off)

hypomethylation/demethylation - activates transcription (gene expression on)

Question 10

How are histones acetylated and deacetylated?

Answer 10

acetylation on lysine of histone

1. histone tail has lysine
2. acetylation: Histone acetyltranscerases (HATs) adds acetyl group making neutral
3. DNA unraveled - euchromatin state
4. deacetylatioN: Histone deacetylases (HDACs) removes acetyl group making positive histone from positive lysine

Question 11

What effect does acetylation and deacetylation has on gene expression?

Answer 11

DNA accessibility depending on structure

Question 12

What is heterochromatin? What is euchromatin?

Answer 12

heterochromatin - structure when acetyl group not added
–> tight structure of DNA bound around histones
–> DNA inaccessible = gene inactive

euchromatin - stricture when acetyl group is added
–> looser structure of DNA bond around histones
–> DNA accessible - genes active
–> acetyl group negative + lysine positive = neutral histone –> less attractive between DNA and histone

Question 13

What is transgenerational epigenetic inheritance?

Answer 13

early life experiences exert longhorn effect on the gene expression which can be inherited by offspring

epigenetic marks (DNA methylation, histone modification) can be acquired on the DNA of one generation and stably passed on through gametes to the next generation. experiences and environmental exposures can change the way your NA works (Without changing the DNA itself) and this could be passed on to your offspring

Question 14

What is the GR protein?

Answer 14

glucocorticoid receptor transcription factor that binds with corticosterone, stress-dealing hormone - cortisol in humans)

Question 15

What is the relationship between grooming and:

anxiety
corticosterone
glucocorticoid receptors
methylation of promoter
and gene expression?

Answer 15

low grooming:
- hypermethylation of promotor for Nr3c1 gene that codes for GR protein
- hypermethylation means genes inaccessible so transcription factor NGFI-A can’t bind to allow GR expression
- low GR expression so corticosterone remains high in cell instead of being removed
- causes high anxiety and stress

high grooming:
- no methyation
- NGFI-A transcription factor can bind to promote of Nr3c1 gene
- high levels of GR expression
- GR can remove corticosterone
- low corticosterone levels
- low anxiety

*when pups are switched, epigenetic markers change
- female pup raise their offspring the way they were raised
- when relaxed, high-nurtured rate was injected with methyl tags –> anxious rat

Question 16

What is the effect of maternal care on behaviour of monkeys?

Answer 16

1. separate some baby monkeys from biological mother - some raised by mother and some by surrogate (human nurse)
2. raised by mother: normal, repulsed by alcohol
   raised by surrogate: aggressive (towards humans and monkeys) anxious, alcoholics
3. methylation pattern is OPPOSITE

Question 17

How are human diseases, disorders, and behaviours linked to epigenetics?

Answer 17

schizophrenia, anxiety, depression, drug addiction

deregulation of acetylation causes anxiety
HDAC inhibitors for Anxiety disorders

Question 18

How are DNMT inhibitors and CRISPR-dCas9 are being used in epigenetics?

Answer 18

• hypermethylation of promoter region by DNMT of tumour suppressor gene done by cancer cells

use DNA methylation inhibitor to target promoter so that tumour suppressor gene will be expressed

1. use dead CRISPR-Cas9 linked with guide RNA which takes it to the promoter
2. scientist links DNMT3A with Cas9 to hypermethylate
3. scientists link TET1 with Cas9 to hypomethylate

Question 19

What is the importance of our epigenetic clock?

Answer 19

• body parts aren’t all the same age
• chronological vs biological age
• epigenetic age acceleration
• biomarker for disease (see age for each organ)