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 Acetylation
Acetylation is correlated with gene activity (universally)
- reduces positive charge of histones, neutralises positive lysines, decreases attraction
between histones (+) and DNA (-)
- acts as docking site for other proteins, e.g. bromodomain proteins, that themselves
open the chromatin (chromatin remodellers) or recruit them

Bromo
ac

Histone Acetylation

Histones are acetylated by histone acetyltransferases, and acetyl groups are

removed by histone deacetylases
HAT (KAT) 18 different genes in mouse
HDACs 18 different genes in mouse

Histone Acetylation

Arguably not an epigenetic modification, rather just a chromatin modification

- due to the rapid acetylation/ deacetylation dynamics (circadian rhythm)
- lack of mechanism for mitotic heritability

Histone Methylation

Histone methylation does not alter the charge

of the histone

Histone methylation can correlate either with

transcriptional activity OR with inactivity

Mono, di and tri-methylation exist

Histone Methylation
H3K9me transcriptionally inactive regions, usually constitutive
heterochromatin, broadly over the whole gene
Laid down by specific lysine methyltransferases, KMTs, with specific activity
for H3K9
Removed by lysine demethylases, KDMs, with specific activity for H3K9me

Histone Methylation
H3K27me transcriptionally inactive regions, more commonly at
facultative heterochromatin, broadly over the whole gene
Laid down by specific lysine methyltransferases, KMTs (e.g. Ezh2, part of
polycomb repressive complex 2, PRC2), with specificity for H3K27
Removed by lysine demethylases KDMs, with specificity for H3K27me3

How do histone modifications influence chromatin

structure?
General rule: modified histone tails are read by other chromatin
proteins; they act as docking sites for other epigenetic factors
- interacting proteins can have the ability to alter chromatin packaging (chromatin
remodellers)
- OR interacting proteins that then bring about other histone modifications

Modified histone tails act as docking sites for

other chromatin proteins
Chromo, MBT
PHD, Tudor

Bromo

me

ac

14-3-3
P

Protein domains that

bind Me, Ac or P at
specific residues

Modified histone tails act as docking sites for

other chromatin proteins

H3

CHD1

HP1

me

me

K
4

CBX2

me

Proteins that bind

Me, Ac or P at
specific residues

27

3 examples of chromodomain proteins

1. CHD1 ATP-dependent chromatin remodeller
2. HP1 - essential heterochromatin protein, can recruit DNMT1
3. CBX2 part of polycomb repressive complex that lays down
H2AK119ub, another epigenetic mark

HP1 binds H3K9me3

HP1 can recruit DNMT
HP1 can recruit HMT to
maintain and spread the
H3K9me3 mark
DNMT can recruit HDAC

Example, incompletely
understood regarding hierarchy

Summary