Tetrahymena Histone Acetyltransferase A: A Homolog to Yeast Gcn5p Linking Histone Acetylation to Gene Activation

TLDR

The study reports cloning of Tetrahymena histone acetyltransferase type A (HAT A). The cloned Tetrahymena HAT A and yeast Gcn5p share conserved active‑site residues and a bromodomain, suggesting chromatin‑directed acetyltransferase activity. Recombinant Gcn5p exhibits HAT activity, and the conserved bromodomain in HAT A indicates targeted histone acetylation that directly links acetylation to gene activation.

Abstract

We report the cloning of a transcription-associated histone acetyltransferase type A(HAT A). This Tetrahymena enzyme is strikingly homologous to the yeast protein Gcn5, a putative transcriptional adaptor, and we demonstrate that recombinant Gcn5p possesses HAT activity. Both the ciliate enzyme and Gcn5p contain potential active site residues found in other acetyltransferases and a highly conserved bromodomain. The presence of this domain in nuclear A-type HATs, but not in cytoplasmic B-type HATs, suggests a mechanism whereby HAT A is directed to chromatin to facilitate transcriptional activation. These findings shed light on the biochemical function of the evolutionarily conserved Gcn5p-Ada complex, directly linking histone acetylation to gene activation, and indicate that histone acetylation is a targeted phenomenon.