Epigenetics refers to the regulation of genomic functions, including gene expression that are brought about by changes in DNA methylation and/or histone tail modifications. These two epigenetic mechanisms work in concert, with alterations in DNA modification affecting chromatin conformation and vice versa. In part epigenetic modifications are inherited, but unlike the genome itself, they are cell specific, plastic, and responsive to environmental influences.

Differential post-translational modifications of histone tails by lysine acetylation and methylation, phosphorylation and recently also crotonylation make up the epigenetic code which is responsible for modulation of gene regulation in normal cell differentiation and in disease.

The Epigenetic probe project aims to generate well characterised tool compounds ‘probes’ against key enzymes and recognition domains involved in histone regulation of transcription and provide them freely to the scientific community to increase the knowledge of these proteins in biology and disease.

Susanne Müller-Knapp is the Project Manager for the Oxford site, which focuses on inhibitors involved in modification and recognition of modified lysines in histones, namely histone lysine demethylases,  Bromo- and  Tudor domain containing proteins. Bromodomains are small protein recognition domains, which mainly bind acetylated lysine, whereas Tudor domains recognize methylated lysine. Histone demethylases are the most recent family of histone-modifying enzymes discovered that remove methyl groups from the terminal amine of histone lysine residues. 

The group establishes and runs cell based assays for the different epigenetic targets to test the in vitro characterised tool compounds for cellular activity.