HISTONE ACETYLTRANSFERASE ACTIVITY IS CONSERVED BETWEEN YEAST AND HUMAN GCN5 AND IS REQUIRED FOR COMPLEMENTATION OF GROWTH AND TRANSCRIPTIONAL ACTIVATION

Yeast and human ADA2 and GCN5 (y- and hADA2 and y- and hGCN5, respecti vely) have been shown to potentiate transcription in vivo and may func tion as adaptors to bridge physical interactions between DNA-bound act ivators and the basal transcriptional machinery. Recently it was shown that yGCN5 is a histone acetyltransferase (HAT), suggesting a link be tween enzymatic modification of nucleosomes and transcriptional activa tion. In this report, we demonstrate that hGCN5 is also an HAT and has the same substrate specificity as yGCN5. Since hGCN5 does not complem ent functional defects caused by deletion of yGCN5, we constructed a s eries of hGCN5-yGCN5 chimeras to identify human regions capable of act ivity in yeast. Interestingly, only the putative HAT domain of hGCN5, when fused to the remainder of yGCN5, complemented gcn5(-) cells for g rowth and transcriptional activation. Moreover, an amino acid substitu tion mutation within the HAT domain reduced both HAT activity in vitro and transcription in vivo. These findings directly link enzymatic his tone acetylation and transcriptional activation and show evolutionary conservation of this potentially crucial pathway in gene regulation.