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

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

miRNAs post-transcriptional gene silencing

Commonly used for experimental knockdown/ RNAi in many labs around the world

S T OP

GO

~1000 genes involved in epigenetic control REGULATORS

~25-30,000 other genes

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.

Using miRNAs for research purposes

Screen for function using miRNAs against each potential epigenetic modifier

brain

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