CHAPTER 2: Enzyme and Protein Families that Regulate Histone Modifications and Crosstalk

The genetic material of nearly all eukaryotes is maintained in the nucleus in the form of chromatin, which consists of DNA wrapped around histone proteins. The histone proteins have the potential to undergo an impressive variety of post-translational modifications, the establishment and removal of which is catalysed by a large number of different enzymes. Modified histones affect chromatin function both directly, by inducing structural change, and indirectly, by recruiting effector protein complexes which contain modification-specific binding domains. Chromatin-based processes such as transcription and DNA repair can also impact on the local histone modification milieu, making the chromatin landscape a complex and dynamic one. No single histone modification functions in isolation; there is a network of interactions between the proteins which establish, remove and bind to modified histone residues, creating extensive crosstalk between the modifications. Epigenetic mechanisms including alterations to histone modifications are known to be involved in many human diseases, so understanding this complex system is likely to present many novel targets for pharmaceutical therapies.