Lecture notes
Epigenetics
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- University Of Portsmouth (UoP)
Document about epigenetics
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EpigeneticsKey Words:
o Epigenetics = refers to the existence of a second non-genetic system at the cellular
level, that regulates gene expression (Haig, 2004 and Griffiths & Statz, 2013).
o Histone = a protein that provides structural support to a chromosome.
o Methylation = indicates the addition of a methyl group on a substrate.
o Chromatin = a substance within a chromosome consisting of DNA and protein.
o Acylation = the process of adding an acyl group to a compound.
o Mirror neuron = a brain cell that reacts both when a particular action is performed
and when it is only observed.
o Trichostatin = an organic compound that serves as an antifungal antibiotic and
selectively inhibits class 1 and 2 histone deacetylase (HDAC) families of enzymes, but
not class 3.
o Nucleosome = the basic structural unit of DNA packaging in eukaryotes.
Key Studies:
Oberlander et al (2008): codes for the glucocorticoid receptor were observed in the
umbilical cord of infants whose mothers suffered from depression in the third
trimester, this epigenetic modification was associated with elevated past stress
salivary cortisol in the 3month old infants = they were affected by their mother’s
depression. There is a relationship between NR3C1 gene expression levels in the
umbilical cord, brain and HPA axis (hypermethylation of the NR3C1 gene)
(biomarkers).
Koenen et al (2011): most individuals don’t develop PTSD even after severe trauma,
the number of traumatic events influenced PTSD risk but only in the p’s showing low
methylation of the serotonin transporter gene (SLC6A4) = gene specific methylation
patterns may offer potential molecular signatures of increased risk for or resilience
to PTSD (biomarkers).
Oberlander et al (2008): chromatin extracted from peripheral blood contains
epigenetic marks that reflect life experiences = enables researchers to easily access
epigenetic markers for stress and vulnerability for mental and neurological diseases
(biomarkers).
Horvath (2013): DNA methylation can be used as a predictor of age – “epigenetic
clock”.
Fagiolini et al (2009): epigenetic research shows the missing link between experience
and the genome in sculpting neural pathways, especially in the critical period of
plasticity.
McCarthy & Arnold (2011): variability in the degree to which brain regions are
masculinised or feminised in one individual results in a mosaic of maleness or
femaleness and greatly increases variance between individuals of the same sex =
need to consider everything.
, Ferrari et al (2013): the epigenetic hypothesis could account for the variation and
plasticity in mirror neuron properties.
Jessberger et al (2007): epigenetic relevant molecules can affect abnormal
neurogenesis and cognitive deficits resulting from seizures.
Cassel et al (2006): neurogenesis can be altered by exposure to antidepressants or
abuse of drugs.
Weaver et al (2004): molecular pathways of maternal care:
- in rats, low licking and nursing activity by mothers altered offspring methylation
patterns at the glucocorticoid receptor gene in the hippocampus = increased HPA
axis response and female offspring who experienced less licking also licked their
offspring less.
- when giving pups of a non-caring mother to a foster caring mother the DNA
methylation phenotype reflected the foster mother, the phenotype maintained into
adulthood.
- central infusion of trichostatin removed group differences in: histone acylation,
DNA methylation, NGFI-A binding, GR expression, HPA axis response = epigenetic
differences were removed with the trichostatin drug.
= emphasis on critical period for the effects of early life experience on methylation
patterns in the hippocampus.
= epigenetic modifications are stably encoded during early life experiences through
behavioural programming.
= the epigenetic state of a gene can potentially be reversible (Roth et al, 2009).
McGowan et al (2009: compared the brain tissue of 2 groups of suicide victims (1
experienced abuse and the other didn’t) – found decreased levels of glucocorticoid
receptor mRNA in the abused group (resulting from higher levels of DNA methylation
of the regulatory region of the glucocorticoid receptor).
- early life experiences were the key factors to explain the alteration of DNA
methylation in crucial genomic regions of the brain
= epigenetics marking itself can be seen as a “persistent form of cellular memory”,
memories of past environmental events are fixed on the genome.
Meloni (2014): epigenetics goes into modern biology and have the potential to
reformulate the biology/society debate.
Labrie et al (2012): epigenetic modifications of DNA and histone proteins may
contribute to complex phenotypes. Inherited epigenetic factors are particularly
stable and have regulatory roles in genomic activities = epigenetics as a promising
path in etiological studies of psychiatric disease.
Notes:
DNA – (transcription) – RNA – (translation) – amino acid chain – protein
The “missing heritability” case:
Completion of the human genome project in 2003 revealed the view that the gene is
a discrete and autonomous agent that powerfully leads traits and development is a
fantasy
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