HAT discovery: Heading toward an elusive goal with a key biological assist

Eukaryotic genomes are maintained within DNA-protein complexes called chromatin. Post-translational modification of chromatin proteins, and especially acetylation of the core histone amino-terminal tails, has long been associated with chromatin assembly and the regulation of gene expression. It is now well accepted that an elaborate array of enzymes are responsible for posttranslational chromatin marks including acetylation and methylation among others and that together they have profound effects on gene regulation. However, this was not always the case. Here we describe the events surrounding the initial identification of GCN5 as a histone acetyltransferase from Tetrahymena thermophila and the discovery that it is an ortholog of a transcription co-activator complex in yeast. This discovery was the first to directly link a well-described transcription factor and histone modifying activity.