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What is Epigenetics

Any heritable difference in the phenotype of a cell or an organism that doesn't result from changes in nucleotide sequence of DNA


Epigenetic Marks

Modifications to DNA or Histone proteins
- Methylation
- Acetylation
- Phosphorylation
- Ubiquitination


DNA Methylation

Most likely on Cytosine
Occurs in mammals at CpG
Occurs in plants at CpG or CpNpG
Initiated by DNA methyl transferase
Maintained in dividing cell by Maintenance methyl transferase


CpG Dinucleotides

Fewer CpG than expected due to DNA repair after deamination
Normal C deaminated
- converted to U
- incorrect base then repaired
5-methyl C deaminated
- converted to T
- harder to ID as incorrect
- CpG converted to TpG



Proteins found in eukaryotic cell nuclei that package and order the DNA
Tails are:
- about 20 aa
- flexible
- charged
- protrude between wrapped DNA


Histone Methylation

Lysines and Arginines in tail
More than one methyl group per lysine tail
More than one lysine per tail can be methylated
Groups added by Histone methyl transferase
Removed by Lysine-specific demethylase 1


Histone Acetylation

Occurs in lysines only
One acetyl group per lysine
Can be multiple acetyl groups per tail
Acetylated lysine cant also be methylated
Acetyl added by histone acetyl transferase
Removed by histone de-acetylase


Phosphorylation and Ubiquitination

- serines
- kinases add P
- phosphatases remove P
- lysine
- 76 aa protein
- added by ubiquitin conjugating enzyme


The Histone Code

Message sent by histone marks
Controls chromatin
Histone marks determine whether chromatin will be condensed or not
More methylation means more condensed
Each modification acts as a binding site for effector molecule


Difference between Heterochromatin and Euchromatin

- nucleosomes tightly wound
- condensed
- inactive
- nucleosomes loosely wound
- active


Why does tightly wound chromatin prevent expression?

DNA binding molecules cannot get access to the DNA


How does DNA methylation alter gene expression?

Preventing access of DNA binding proteins
If methyl groups present then DBP cant bind and cant:
- direct transcription
- cause cis-acting elements to be brought into contact with intended target


What happens with Gametogenesis?

Period of genome wide re-programming of methylation
De-methylation occurs early in development of primordial germ cells
Male and female cells regain their methylation at different times
Re-methylation is complete in both prior to meiosis



After fertilisation embryo again de-methylated
- paternal = actively
- maternal = passively
Both re-methylated at implantation
Done to remove any additionally required methyl groups



Some genes dont get reprogrammed the same as others
Usually genes that act differently depending on whether from father or mother
In a female, both alleles of an imprinted gene will be re-set to match the methylation pattern she received from her mother
In a male, both alleles of an imprinted gene will be re-set to match the methylation pattern he received from his father


Prader Willi and Angelman's Syndrome

PWS and As genes in 2Mb imprinted region on chromosome 15
In normal child:
- only paternal PWS allele expressed
- only maternal AS allele is expressed
PWS will occur if paternal PWS allele is missing
AS will occur if the maternal AS allele is missing


Dosage Compensation

Epigenetic control used to compensate for double dose of X in females
Mammals compensate by inactivating one X chromosome