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

Non-coding RNAs
•  Many classes of small, mid-sized and long noncoding RNAs, only some
of which we will cover

•  MicroRNAs (miRNAs) – post-transcriptional gene silencing

•  Piwi-interacting RNAs (piRNAs) – control transposable elements and

direct DNA methylation at transposable elements

•  Long non-coding RNAs (lncRNAs) – appear to

direct epigenetic machinery and establish
different epigenetic states

1
Non-coding RNAs
•  Many classes of small, mid-sized and long noncoding RNAs, only some
of which we will cover

•  MicroRNAs (miRNAs) – post-transcriptional gene silencing

•  Piwi-interacting RNAs (piRNAs) – control transposable elements and

direct DNA methylation at transposable elements

•  Long non-coding RNAs (lncRNAs) – appear to

direct epigenetic machinery and establish
different epigenetic states

miRNAs – post-transcriptional gene silencing

•  Discovered in C. elegans and plants
•  >1,000 miRNA genes in mammals
•  Each mature miRNA (19-24bp) may target
many genes
•  Drosha and Dicer dependent
•  Repression of translation or mRNA
cleavage
•  Involved in development, differentiation,
cancer and disease

2
miRNAs – post-transcriptional gene silencing
•  Commonly used for experimental
knockdown/ RNAi in many labs
around the world

ST OP
GO

~1000 genes involved in

epigenetic control
~25-30,000 other genes
REGULATORS

Which genes are involved in epigenetic modification of the genome,

in different scenarios?

We use microRNAs engineered against each of the ~1000 epigenetic modifiers

to reduce the expression of each, and test their roles in different cell scenarios.

3
Using miRNAs for research purposes
Screen for function
using miRNAs against
each potential brain
epigenetic modifier

ES cells

Potential epigenetic
modifiers blood system

X inactivation

Acknowledgements
Rnai diagram retroviology (microRNA biogenisis and action) (http://
en.wikipedia.org/wiki/File:Rnai_diagram_retrovirology.png) by Anne
Saumet and Chales-Henri Lecellier CC BY 2.0 (http://
creativecommons.org/licenses/by/2.0/deed.en), via Wikimedia
Commons