Mechanisms of Histone Modifications

This chapter focuses on epigenetic mechanisms involving histone modifications and recent development establishing a link between chromatin modifications (with an emphasis on acetylation and methylation) and cellular processes such as transcription and DNA repair. It includes all features such as chromatin and DNA modifications that are heritable and stable over rounds of cell division, but do not alter the nucleotide sequence within the underlying DNA. Chromatin modifications act in a coordinated and orderly fashion to regulate cellular processes such as transcription, DNA replication, and DNA repair. These processes may be regulated by TRRAP/histone acetyltransferases (HAT) and there is an intimate and self-reinforcing cross-talk and interdependence between histone-modifying complexes and other histone-modifying activities such as acetylation, phosphorylation, and methylation. Consistent with the critical function of histone modifications in key cellular processes, a large body of evidence has suggested that these complexes are intimately linked to human pathologies. Most notably, recent genetic and molecular studies have directly implicated histone modifications and histone-modifying complexes in human cancer. The fact that epigenetic alterations are, in contrast to genetic changes, reversible, has important implications for human cancer treatment, as aberrant histone modifications are potential molecular targets for therapeutic intervention in human malignancies.