Changes to gene expression that do not result from mutation

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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

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

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

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

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

Transcription factor Promoter region Methylation © 2016 Paul Billiet ODWS

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

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

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

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

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