epigenetics topics - cocaine addiction, obesity, Angelman syndrome

1. EPIGENETICS
Drug Addiction, Obesity and
Angelman Syndrome

2. What is Epigenetics?
 Nature v. Nurture
 The controlled expression of genes
 Methylation
 Acylation
 Histone protein modifications - h2a h2b h3 h4
 Chromatin remodelling
 Promotor genes

3. How Does it Affect Drug Addiction
Cocaine
 Chronic and relapsing brain disease due to compulsive drug
seeking and usage.
 Gene expression changes in the reward region of the brain –
Nucleus Accumbens
 Genes: cdk5 and bdnf (brain-derived neurotrophic factors)
 Chromatin structure is changed: acetylation by histone
acetyltransferase and histone deacetylases
 Acetylation on histones H3 and H4 reduces electrostatic interaction
between histone protein and DNA, relaxing Chromatin structure and
therefore making DNA more accessible to transcriptional regulators.
 ∆fosB – transcription factor involved in behavioural responses
 Starts to accumulate when chronically exposed to cocaine – spiking
dopamine levels and leading to addiction.

4. Epiobesogenes
FYN
Hypermethylated
AMPK is
phosphorylated
Lipid synthesis
Preadipocyte
differentiation
Obesity
Hypomethylated
FYN-GTPase
PIKE-A complex
Phosphorylates
STAT5a
STAT5a
activates PPARγ
ADIPOQ
Hypermethylated
PPARγ cannot
bind
Adiponectin
protein not
transcribed
Retention of fatty
acids
Obesity
Hypomethylated
PPARγ binds
Adiponectin
protein
transcribed
Fatty acid
catabolism
Weight loss
Cholesterol
transporter genes
ABCG1
Cholesterol efflux
Maternal NEFA
not transported
into adipocyte
NEFA not
esterified
Children not
obese
ABCA1
Cholesterol influx
Maternal NEFA
transported into
adipocyte
NEFA -> EFA
Obesity in
children
How Does it Affect Obesity?
 Definition of obesity: hypertrophy and hyperplasia of
white adipose tissue
X
1
2
4
5
3
Insulin
supresses
X
X
6 7

6. How Does it Affect Angelman
Syndrome?
 Neurodevelopment disorder
 Caused by disruption of UBE3A
gene
 Loss of gene OCA2 associated
with light-coloured hair and fair
skin
 Imprinting disease- alterations in
DNA methylation
 Most effective method of
diagnosis is Methylation test

7. Conclusion
 Nature vs Nurture: which has more of an
effect?