1. Changes to gene expression that do not result from mutation
EPIGENETICS
Changes to gene expression that do not result from mutation
© 2016 Paul Billiet ODWS

2. DNA methylation Switching genes into the “off” position
Embryonic development
X-chromosome inactivation
Gene imprinting.
© 2016 Paul Billiet ODWS

3. X-chromosome inactivation
Tortoiseshell cats are female
© 2016 Paul Billiet ODWS

4. DNA methylation - discovery
Methylation was inhibited when cytidine analogues are used
DNA methyltransferase (DNMT) inhibited
So methylation acts at cytosine residues  methylcystine
Where C is next to G (CpG sites) so:
© 2016 Paul Billiet ODWS

5. Methylated promotors Methylation Gene to be translated Promoter region
© 2016 Paul Billiet ODWS

6. Transcription factor Promoter region Methylation
© 2016 Paul Billiet ODWS

7. Seeing methylation Immunofluorescence of Hela cells.
Methylcytidine in red
Tubulin in green
© 2016 Paul Billiet ODWS

8. CpG islands
CpG islands (CGI) exist in the genome that act as initiators for genes
CpG in islands tend NOT to get methylated
CpG islands destabilise nucleosomes – DNA unwinds for transcription
When CpG islands get methylated, the gene they control is switched off
This may lead to inappropriate gene silencing.
© 2016 Paul Billiet ODWS

9. Methylation & cancer
Hypomethylation can cause oncogenes to become active Hypermethylation can lead to de-regulation of cell cyle (Inappropriate gene silencing) Silencing tumour supressor genes.
© 2016 Paul Billiet ODWS

10. Methylation & epigenetics
Methylation is copied when the DNA is replicated
Methylation is hereditary
But why?
Conflict between parental genomes? Conflict over use of resources Few big fetuses v many little fetuses
Egg laying v placental implantation? Avoiding accidental activation of sex cells.
© 2016 Paul Billiet ODWS