Chromatin modifying enzymes: their function and role in cancer

Helena Santos-Rosa, Antonis Kirmizis, Chris Nelson, Claire Pike, Sophie Deltour and Tony Kouzarides

Gurdon Institute, Cambridge University, Cambridge, UK

Modifications of chromatin play important roles in many biological processes. In addition, the miss-regulation of chromatin modifying enzymes has been implicated in the genesis of cancer and drugs against such enzymes are now in the clinic. We are interested in defining the molecular mechanism by which modifications function and identifying more enzymatic activities that modify chromatin. Recently we have identified proline isomerisation as a novel non-covalent modification on histones in yeast. We have now characterised proline isomerases that function to modify human histones and find that they are implicated in cancer. We have also defined a novel enzymatic activity that is able to cleave the tail of histone H3 at a specific site. This activity appears to be necessary for the correct displacement of H3 at promoters, during the process of transcriptional activation.