Lecture 13 Stress & Epigenetics Flashcards
Space and genes
Identical twins
One spends 6 months in space
7% different now
DNA Basics
- All cells contain all DNA
- All start as stem cells
- Differentiation due to epigenetics
- This is usually one way
2m of DNA/cell
DNA structure
Double helix wound around histones
Chromatid = call DNA surrounded by its histones
Each nucleosome is 8 histones and a DNA strand
Acetyl & methalation
Adding an acetyl group causes unwinding and greater access for transcription
Methylation causes more tight binding and inactivation, it cannot be transcribed
Transcription fate/control
Transcriptional diversity: cell fate specification Stable -Early on -Prenatal in humans, postnatal in rats -Permenant -involves differentiation -Is like organization
Transcriptional control -Later -Less black and white Dynamic -Turned on and off
DNA methylation: the addition of a chemical modification (CH3)
- DNA methylation reduces DNA expression
- Reduce transcription factors ability to bind at promoter regions
- Attract proteins that influence tighter DNA coiling
Epigenetics:
Functional modifications to the genome
That do not alter the underlying sequence
DNA and epigenetics are complimentary, working together to define each of us
Is this heritable??
Features of the epigenome are established very early development however parts of the epigenome have the potential to be dynamically regulated
Mostly the epigenome gerts wiped at zygotic phase
But not so clear, rats inherit info about danger
The Epigenome
Multiple levels of transcriptional control
Multiple levels of transcriptional control
DNA methylation
- Hydroxymethylation (5hmc) of a cytosine
- Transcription factors cannot bind
Histone variants
- Different bundling
- Harder/Easier to trancribe
Histone post-translational modifications
- Acetylation of histone tale opens DNA
- Deacetylation opposite effect
DNA methylation (5mC)
Typically associated with turning genes “off”
- X inactivation
- Females only use one of the two copies of genes on the –X chromosome
- One silenced with methylation
- They only use one copy of each gene (some from each chromosome)
Imprinting
- Gene on both X and Y, but only need one input
- One parent silenced with methylation
Observations from “house-keeping genes”
- Required for ALL cells to function
- Low levels of methylation
Therefore, Methylation = low gene expression
Ice Storm Study
1998 ice storm
Many people without power for days
Very cold
Pregnant mothers
Children followed
Used the SDQ - strength and difficulty questionnaire to measure kids emotional/behavioral issues
At all ages, those kids born to mothers who went through the ice storm (and so were stressed) have higher SDQ scores
Good rat moms… (2 things)
Rat moms:
(1) Spend time in arched back nursing posture
(2) Licks/grooms kids
Kids cant pee or poop without stimulation so this helps them
Also has an epigenetic effect
Care in rat moms is operationalized by
daily observation of the mom’s lick/grooming behavior
Licking and grooming:
model of early life adversity
Experiment and results
Michael Meany’s group
Separate mothers on licking and grooming
Body and anogenital licking
Rate LG behavior
Top 25% compared to bottom 25%
Both high and low LG mothers adequate
Pups survive to adulthood
Adult offspring of high LG mothers:
decreased startle responses
increased exploration in novel environments
shorter latencies to eat novel food
Reduced stress response in adulthood
Adult offspring of low LG mother:
neophobia
higher startle response
more probe burying
Increased stress response in adulthood
Transgerational effect of maternal care
How does maternal care change anxiety (gene or environment)?
How does this influence parenting?
Human context: maternal behavior somewhat consistent in families
- Cross fostering studies: is this genetic or learned?
- Switch pups from high and low LG mothers
Created 8 combos
(1) High mom/Her pups (control)
(2) High mom/separated and return pups (to see if separation causes it)
(3) High mom/ pups of another high mom (see if raising someone else’s pups changes it)
(4) High mom/low mom’s pups
Same again for low mom’s
High mom with low ids and low mom with high mom’s kids were experimental group
RESULTS
High raised by low = increased anxiety (no exploration of new area)
Low raised by high = low anxiety
CONCLUSION
It is the environment, not the genes
Do they pass this on?
Rats raised low, parent low
Rats raised high, parent high
SO these effects continue lifelong, even after separation to their own cages at 21 days
Licking/Grooming effect on stress system?
More Licking/Grooming results in lower response to stress
How??
Corticosterone released in response to stressor
Negatively correlated with maternal LG (r = -0.61)
Fewer glucocorticoid (GR) receptors in the adult brain of low LG offspring
In the hippocampus (memory)
The hypothalamus and pituitary as well
Longterm changes in protein production based on maternal care
