The study of post-translational modification (PTM) of lysine and/or arginine residues in histones and other proteins through methylation and acetylation has led to the discovery of three classes of epigenetic proteins:-
- Those which add a methyl or acetyl group (writers) using S-adenosylmethionine (methylation) and Acetyl-CoA (acetylation) as co-factors. Histone methyltransferases catalyze the transfer of up to three methyl groups to the e-amino group of a lysine residue or up to two methyl groups to the guanidine group of an arginine residue. In the case of arginine methylation, dimethylation can occur in a symmetrical or unsymmetrical manner. Acetylation of lysine residues only occurs once and arginines are not acetylated.
- Those which remove a methyl or acetyl group (erasers).
- Those which bind histones/proteins containing a particular PTM (readers).
Each of these classes of epigenetic proteins contributes to the control of various genes and the goal of the Epigenetic Probes Project is to unravel the biology of these proteins by developing small-molecule inhibitors and antagonists with the following properties
- IC50 or Kd < 100nM
- Selectivity > 30-fold over proteins in the same family
- Significant cellular activity below 1 microM