Behavioural Genetics GENE3733
Epigenetics
• All cells have exactly the same DNA – epigenetics helps with cell differentiation
• Studying heritable changes of DNA, that regulate gene expression
• No change in DNA sequence!!
• 2 forms of info in cell:
• Genetic info à genome à DNA à stable and fixed à info for the manufacture of all proteins needed
• Epigenetic info à epigenome à flexible!! à additional instruction on how, when and where the info should
be used
Genetics vs Epigenetics
Signals
• Epigenome changes based on signals
• From inside the cell, from neighbour cells, from environment
• Signals
• Direct contact
• Nervous system development
• Short distance factors
• Blood clotting
• Long distance factors
• Hormones
• Environmental
• Can be all 3
The epigenetic landscape
MZ twins
The epigenome of
MZ twins
The epigenome
• Gene’s function à determined by developmental and environmental history of the cell
• Genomic DNA exist in chromatin configuration
• Epigenome is established through folding of DNA into chromatin
• Chromatin structure with its covalent modifications provide epigenetic regulation
• Modifications à methylation / histone modification
• Epigenome = layer of info on top of the DNA sequence
• Greater plasticity than genome; much less stable
• Mediate penetrance and expressivity
Chromatin organizes and
compacts DNA
Nucleosome
ac ac
ac ac
DNA
methylation ac
from Horn and Peterson Science, 2002
Chromatin structures
• Types of chromatin
o Euchromatin
• Transcriptionally active, less compacted
o Heterochromatin
• Less transcriptionally active, very compacted
Nucleosomes prevent expression
Inheritance
• May be passed to daughter cells
• As cells grow & divide à epigenetic tags are copied along à especially important
during embryonic development
• Used to think that
every newborn’s
epigenome is
erased à not true!!
Genomic imprinting
• Unequal expression of maternal & paternal alleles
• Easier to detect dysregulation in imprinted genes
• Activity of the gene is modified depending on gender of transmitting parent
• Inherit only one working allele à one from other parent is epigenetically silenced
(methylation during gamete formation)
• Very sensitive to environment à only one active copy and no back-up
• Environmental signals can effect imprinting process à hormones & toxins during
pregnancy
Genomic imprinting
Prader-Willi Angelman
• Chromosome 15 • Chromosome 15
• Missing allele activity from dad • Missing ellele activity from mom
• Dad’s copy is missing / 2 maternal copies • Mom’s copy is missing / 2 paternal copies
X-inactivation
Rainbow and Copycat
• Cloned cat: Genome is identical
• Yet looks different from mother
Proving epigenetic inheritance
• Rule out possibility of
genetic changes
• Show epigenetic effect
can pass through
generations à rule out
environmental exposure
Epigenetics & Evolution
• Genome
• Changes slowly through process of random mutation & natural selection
• Takes many generations to spread trait in population
• Epigenome
• Changes fast
• Flexible as environment changes
• Can happen in many individuals at once
• Epigenetic inheritance may allow individual to continue to adjust gene expression
to fit environment, without changing DNA
