26 - Nature, Nurture, and Epigenetic Regulation Flashcards
What does “epigenetics” mean?
Above the genome
What are some processes involved in epigenetics?
Histone acetylation, histone methylation, and DNA methylation
True or false: histone acetylation, histone methylation, and DNA methylation are all distinct events
False: they are all interconnected
What is epigenetics?
Modifications on the genome
How come epigenetics is interconnected?
The proteins and enzymes that carry out histone acetylation, histone methylation, and DNA methylation are all influenced by the state of histones/DNA
What can you say about genes that are packed in heterochromatin?
They are not expressed
What can you say about genes that are packed in euchromatin?
They are expressed
What does the chemical modifications of histones/DNA influence?
Chromatin structure, and gene expression
What happens during histone acetylation?
Acetyl groups are added to lysines on histone tails
What is the charge on lysine?
Positive
What is the effect of histone acetylation?
Loosens chromatin structure, thus allowing for transcription
What is the effect of histone methylation?
It condenses chromatin
What is the effect of phosphorylation of histone methylation?
If it is next to a methyl group, it can promote transcription by loosening chromatin structure
When can phosphorylation lead to loosening chromatin structure?
When it is next to a methylated amino acid
True or false: epigenetic information can be inherited
True: these modifications can be inherited through DNA replication
What is epigenetic inheritance?
The transmission of information that is not in the DNA sequence
Where do modified histones go during DNA replication?
To both duplicated chromosomes
True or false: chromatin modifications alter the DNA sequence
False: they alter the epigenome, not the DNA sequence itself
Where does DNA tend to be methylated?
At CpG sites
What is a CpG site?
A cysteine adjacent to a guanine
What is the importance of a CpG site?
It is the site where DNA is most likely methylated
What does DNMT stand for?
DNA methyltransferase
What does DNMT do?
Adds a methyl group to DNA
True or false: location in the nucleus does not influence transcription
False: the location can also influence transcription
What is the usual state of perinuclear heterochromatin?
Usually silenced
How can perinuclear heterochromatin be expressed?
By being close to nuclear pores
How come perinuclear heterochromatin close to pores can be expressed?
They are close to activator systems
What do activator systems in the nucleus do?
Recruit transferases to open up heterochromatin
Where are activator systems found?
Close to nuclear pores
What can you say about chromatin right around the nucleolus?
It tends to be silenced
True or false: the chromatin structure is the same throughout the nucleus
False: the structure can alter throughout the nucleus
What is a transcriptional factory?
A place where multiple genes from different chromosomes can be transcribed together
How are multiple genes on different chromosomes transcribed together?
Through transcriptional factories
True or false: identical twins can diverge
True: based on epigenetics, there can be changes in appearance and health
What do identical twins have in common?
They have the same exact DNA
How are identical twins made?
They come from the same egg (clones)
True or false: if one identical twin gets cancer, the other twin must get cancer
False: there are differences in their epigenome
What did the mice in the NOVA video have in common?
The same DNA
What did the mice in the NOVA video have differently?
Different skin color and weight
What gene was affected in the mice in the NOVA video?
Agouti
What does the Agouti gene do?
Determines skin color and weight
What happens if the Agouti gene is constantly activated?
The mouse becomes yellow and fat
What happens if the Agouti gene is inactivated?
The mouse becomes dark and skinny
In the dark and skinny mouse, what is the state of the Agouti gene?
Silenced
In the yellow and fat mouse, what is the state of the Agouti gene?
Activated
How is the Agouti gene silenced or activated?
It is silenced by methylation
What is the genome compared to in a computer?
The hardware
What is the epigenome compared to in a computer?
The software
What controls the type of cells in a tissue?
The epigenome (silence the unneeded genes)
True or false: the epigenome is permanent
False: it can be changed
How can the epigenome of the mice in the NOVA video be changed?
By feeding them a methyl group rich diet
What happens when the mice eat a methyl group rich diet?
They silence the Agouti gene and become darker and skinnier
What is the significance of the methyl group rich diet in the mice?
What you can eat can affect future generations
What was done after the study in mice?
Follow up with identical twins in humans
What was the purpose of the human study in the NOVA video?
To see how close twins are epigenetically
What was the sample of the human study in the NOVA video?
40 twins, age 3 to 74
What was the human experiment in the NOVA video?
Cells were taken from identical twins, and their DNA was compared to analyze the epigenomes
What did the dark pink bands in the NOVA video signify?
Places where genes in the epigenome were turned off
What was found with the epigenomes of young twins?
They had very similar epigenomes
What was found with the epigenomes of old twins?
They had very different epigenomes
What was the conclusion of the human study in the NOVA video?
As twins age, epigenetic differences accumulate (especially when lifestyles differ)
What is the advantage of cancers caused by epigenetics?
They are easier to modify than broken genes
What was the clinical trials in the NOVA video?
A drug that fixed the epigenetic tags in the genes
What was the result of the clinical trials in the NOVA video?
Many patients were improving, with not many side effects
What is the responsibility associated with epigenetics?
It is easy to mess up the epigenome, so it needs to be taken with care (not stuck with inherited genome)
True or false: maternal behavior can affect offspring
True: this is seen in licking and grooming, which is generationally passed on
What does LG stand for?
Licking and grooming
What behavior does high LG lead to?
Relaxed adults
What behavior do relaxed adults go through?
High LG
What behavior does low LG lead to?
Fearful adults
What behavior do fearful adults go through?
Low LG
How can a low LG phenotype be induced?
Through stress
What happens when an animal is stressed?
The adrenal glands release glucocorticoids
What do glucocorticoids do (in the brain)?
Bind to the hippocampus, inhibit the hypothalamus, and inhibit the pituitary gland
What does the hippocampus do under stress?
Inhibits the hypothalamus
What does the hypothalamus do under stress?
Cannot activate the pituitary gland through CRF
What does the pituitary gland do under stress?
Cannot activate the adrenal glands
What happens after glucocorticoids are released by the adrenal glands?
The production is quickly shut off by the negative feedback to the adrenal gland
Why do glucocorticoids induce a negative feedback response?
It reduces a long-term, chronic stress response
How does high LG affect GR receptors?
There are increased GR receptors
How does increased GR receptors impact the stress response?
There is less stress, because there is more inhibition to shut the system off quicker
How does low LG affect GR receptors?
There are decreased GR receptors
How does decreased GR receptors impact the stress response?
There is more stress, because there is less inhibition to prevent a quick shut off
Where are GR receptors found (in terms of the LG stress response)?
On the hippocampus
What does LG behavior control (molecularly)?
Serotonin release
What does serotonin act on (in response to the LG pathway)?
The hippocampus
What is the serotonin pathway to activate the primary response?
Serotonin –> 5-HT7 receptor –> aGs –> AC –> cAMP –> PKA –> CREB –> primary response
What is the primary response of the serotonin pathway?
NGF1-A and AP-2
What are NGF1-A and AP-2?
Transcription factors
Which primary response element controls the GR gene?
NGF1-A
What is the secondary response of the serotonin pathway?
The GR gene
How does serotonin impact GR receptors?
Higher serotonin leads to higher levels of GR
How does DNMT affect the GR gene?
It methylates the DNA where NGF1-A will bind
How does DNA methylation impact the GR gene?
It silences it, since NGF1-A cannot bind to the gene
How does low LG affect the GR promoter?
It leaves it highly methylated, thus silenced
How does high LG affect the GR promoter?
It binds to NGF1-A, thus becoming activated
What is the epigenetic modification of LG?
The methylation of the GR promoter
What leads to the epigenetic modification of the GR gene?
The LG behavior itself
What is meant by cross fostering?
Pups born to high LG moms, but reared by low LG moms, are similar in behavior to low LG pups (and vice versa)
What is the significance of the cross fostering experiments?
They demonstrate that epigenetics can be modified and changed
What does TSA stand for?
Trichostatin
What does TSA do?
Blocks HDAC
How does TSA affect GR expression?
It increases GR expression
How does TSA affect the LG behavior?
It leads to high LG
How does TSA lead to high LG behavior?
It blocks HDAC, so it keeps the GR gene acetylated and activated
What does SAM stand for?
S-Adenosyl methionine
What does SAM do?
Promotes histone methylation
How does SAM affect GR expression?
It decreases GR expression
How does SAM affect the LG behavior?
It leads to low LG
How does SAM lead to low LG behavior?
It promotes histone methylation, so it keeps the GR gene methylated silenced
What is the problem with generalized HDAC/HAT drugs?
They can affect a large range of genes
How can the problem of HDAC/HAT drugs be circumvented?
By targeting specific HDACs/HATs found in specific locations (the synapse)
