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Lecture 9

BIOC14H3 Lecture Notes - Lecture 9: Glucocorticoid, Non-Coding Rna, Epigenome

Biological Sciences
Course Code
Patrick Mc Gowan

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BIOC14Winter2013 Lecture 9: Environmental Epigenetics and Transgenerational Epigenetic Inheritance
The developmental program
o Performationism: the idea that development unfolds without environmental input, developing
from miniature versions of themselves
o Gene centric view: DNA RNA Protein Function ** This is not always true!
o Also influenced other ideas of human developmental stages like Freud and Piaget
o Jean piaget: father of developmental psych, created a developmental steps for cognitive growth,
each step was a foundation for the next
o Freud: predefined stages of development: no reversion
o To date, very little prediction of phenotype or complex disease risk from knowledge of gene
sequence like SNPs
o Genetic data alone is insufficient to explain phenotype needs additional factors
One genome, many epigenomes
o Epigenetic = above the genome
o Epigenetics = the study of changes in gene expression caused by mechanisms other than DNA
sequence variation
o 200+ cell types are generated form a virtually identical genome via epigenetic mechanism
o epigenetic changes can be mitotically or meiotically heritable
Epigenetic landscape
o original meaning role of gene regulation in development
o current meaning combined modifications to DNA (stochastic random , environmenta) that
give rise to phenotype
o same genes but different gene expression phenotypes differ among monozygotic twins
Epigenetic regulation of gene expression
o 3 components of the epigenome:
o 1) histone proteins bound to DNA and regulate accessibility of transcritption factos
o 2) DNA methylation covalently bound to DNA itself an interface between a dynamic
environment and a static genome more DNA methylation means decreased gene expression
(DNA methylation increases with age)
o 3) Non-coding RNA: control the expression of other genes
o epigenetic differences among monozygotic twins increases with age goes hand in hand with the
fact that DNA methylation also increases with age
Classic role of DNA methylation: Transcriptional repression
o DNA methylation blocks transcription factor binding promoters, enhancers etc.
o Increased DNA methylation = decreased gene expression ?
The Histone Code: Covalent modifications of the N terminal tail of histones
Early life adversity and later life mental health
o Suicide a leading cause of death worldwide
o Linked to but not predicted by mental disorders and adversity early in life
o Genetic and non genetic factors contribute
o Changes in gene expression in the brain associate with suicide
The Stress Response
o The HPA axis (hypothalamic pituitary adrenal axis) negative feedback loop

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o Cortisol is in the blood, travels to bran stem and binds, shutting down a further stress response
o Disruption in this feedback results in continued cortisol release resulting in neurotoxicity and
o glucocorticoid receptors (GRs): bind glucocorticoids and inhibit the stress response
o increased GRs = decreased stress response
o more receptors shut down the stress response faster
Programming of gene expression by maternal behavior in rats
o in rats, maternal care consists mainly of licking and grooming (LG)
o rats show natural variations in maternal care
o Adoption studies: baby that is born biologically to a mother who s a high licker and groomer, and
then adopted by low LG mom will still grow to be anxious and have the same characteristics as the
adoptive mother
o high licking and grooming = high GR expression = high GRs = decreased stress response
The stress response
The HPA axis: A negative feedback loop.
Glucocorticoid receptors (GRs): Bind glucocorticoids and inhibit
the stress response. Increased GR = Decreased stress response
The stress response
v v
v v
The HPA axis: A negative feedback loop.
Glucocorticoid receptors (GRs): Bind glucocorticoids and inhibit
the stress response. Increased GR = Decreased stress response
Rats show natural variations in maternal care!
GR gene expression
Programming of Glucocorticoid Receptor
DNA methylation in rats
Mean Methylation
DAY 20
DAY 90
DAY 21
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