Specific epigenetic modifications

DNA methylation
Methylation of 5 group of cytosines within CpG dinucleotides

Post-translational histone modifications

Methylation, ubiquitination, phosphorylation, sumoylation, acetylation of residues in the
N-terminal tails of histones

Chromatin remodelling
ATP dependent chromatin remodelling complexes shift nucleosomes

Histone variants
Histones with varying stabilities or specialist domains that alter the function of the nucleosome

Noncoding RNAs
piRNAs and other siRNAs that can direct epigenetic machinery
Long noncoding RNAs may direct epigenetic enzymes to sites in the genome

Histone Modifications
Post-translational modification of histones
Chemical modification of histone
Acetylation and methylation are best characterised
Ubiquitination, phosphorylation, sumoylation, ADP-ribsolyation, citrullination

Histone Tail Modifications

Most modifications occur on the N-terminal tails that protrude from the
nucleosome, accessible to other chromatin proteins
>50 sites can be modified, some
with more than one type of tag
e.g. Ac or Me
Predominantly on the tails of H3
and H4, fewer on tails of H2A
and H2B

Histone Tail Modifications

Many different post-translational modifications
Different modifications are correlated with different functions
Histone modification

Which residues?

Functions

Methylation (me, mono, di or

tri me)

Lysines (K) and

Arginines (R)

Transcription, Repair (K)

Acetylation (ac)

Transcription, Repair, Replication,

Condensation

Ubiquitination (ub)

Transcription

Sumoylation (su)

Transcription

ADP-ribosylation

Glutamate (E)

Transcription

Phosphorylation (Ph)

Serine (S) and

Threonine (T)

Transcription, Repair, Condensation

Citrullination (Cit)

R converts to Cit

Transcription

Combinatorial Histone Modifications

Many different sites able to be modified a large number of
combinations
The functional outcome of the various combinations is called the
histone code
In theory, we may be able to map and understand the histone code,
and infer outcome based on the histone marks

Acknowledgements

X Inactivation and Epigenetics by Etsuko Uno and Drew Berry, 2012 Walter &
Eliza Hall Institute of Medical Research. Reproduced with permission from
WEHI.