Chromatin-modifying enzymes in transcription and cancer

In recent years, our view of how gene expression is controlled has changed dramatically. The discovery of enzymes that modify histones has revealed that transcription is an enzymically driven process. Such modifications can recruit specific proteins and mediate chromatin changes that affect transcription either positively or negatively. Important biological pathways leading to cell proliferation are under the control of these enzymes, and several of them are found deregulated in cancer. The hope is that chromatin-modifying enzymes will be a rich source of targets for drug discovery. Modifications in chromatin were known to exist for many years, but it was not until 1996 that enzymes which mediate them were discovered. Two pioneering discoveries led the way. Dave Allis and colleagues [1] showed that a yeast transcription factor GCN5 was a histone acetyltransferase and Stuart Schreiber and colleagues [2] identified a histone deacetylase (HDAC1) as the target for trichostatin A, a drug known to regulate of cell differentiation. The identification of these new enzymes catalysed experiments that showed that two well-studied human co-activators {CREB (cAMPresponse-element-binding protein)-binding protein (CBP) and p300 [3,4]} as well as a basal transcription factor (TAF250) [5] possess histone deacetylase activity. These findings established that activation of transcription is not only