Claire Mowbray

• Characterising the sensitivity of super-enhancer hijacked lymphoid malignancies to epigenetic perturbation
• BSc Hons Biomedical Sciences

Epigenetics is an additional layer of instructions on DNA. Super enhancers provide instructions to genes and are defined by the epigenetic mark, H3K27ac. They increase gene expression by laying down H3K4me3 over the genes they control. Genes of interest (n=20) were selected if they had H3K4me3 or H3K4me3+H3K27ac covering their gene-body. 

‘Healthy’ lymphoid cells were treated with increasing concentrations of the drug, A-485, which inhibits the enzyme that lays down H3K27ac. 48- and 96-hours after treatment, gene expression analysis was performed. 

I observed that some genes like PIK3R5 showed a significant decrease in expression when exposed to A-485, but many others did not show a change. There was no difference between genes with H3K4me3 or H3K4me3+H3K27ac covering their gene-body, nor was there any significant change between 48 and 96 hours of exposure. 

Next steps are to look at all the genes in the genome to see if an association exists.

Funded by: Newcastle University Research Scholarship 

Project Supervisor: Dr Lisa Russell, with help from Dr Letizia Marchetti and Phoebe Snow