Open AccessHistone Acetyltransferase Activity Is Conserved between Yeast and Human GCN5 and Is Required for Complementation of Growth and Transcriptional Activation
Author(s) -
Li Wang,
Craig A. Mizzen,
Carol Y. Ying,
Reyes Candau,
Nickolai A. Barlev,
James E. Brownell,
C. David Allis,
Shelley L. Berger
Publication year - 1997
Publication title -
molecular and cellular biology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.14
H-Index - 327
eISSN - 1067-8824
pISSN - 0270-7306
DOI - 10.1128/mcb.17.1.519
Subject(s) - biology , histone acetyltransferase , acetylation , histone , complementation , transcriptional regulation , transcription (linguistics) , acetyltransferase , microbiology and biotechnology , transcription factor , genetics , mutant , biochemistry , gene , linguistics , philosophy
Yeast and human ADA2 and GCN5 (y- and hADA2 and y- and hGCN5, respectively) have been shown to potentiate transcription in vivo and may function as adaptors to bridge physical interactions between DNA-bound activators and the basal transcriptional machinery. Recently it was shown that yGCN5 is a histone acetyltransferase (HAT), suggesting a link between enzymatic modification of nucleosomes and transcriptional activation. In this report, we demonstrate that hGCN5 is also an HAT and has the same substrate specificity as yGCN5. Since hGCN5 does not complement functional defects caused by deletion of yGCN5, we constructed a series of hGCN5-yGCN5 chimeras to identify human regions capable of activity in yeast. Interestingly, only the putative HAT domain of hGCN5, when fused to the remainder of yGCN5, complemented gcn5- cells for growth and transcriptional activation. Moreover, an amino acid substitution mutation within the HAT domain reduced both HAT activity in vitro and transcription in vivo. These findings directly link enzymatic histone acetylation and transcriptional activation and show evolutionary conservation of this potentially crucial pathway in gene regulation.