IDENTIFICATION OF A GENE ENCODING A YEAST HISTONE H4 ACETYLTRANSFERASE

A collection of yeast temperature-sensitive mutants was screened by an enzymatic assay to find a mutant defective in the acetylation of hist one H4. The assay used a fractionated cell extract and measured acetyl ation of a peptide corresponding to amino acids 1-28 of H4. There are at least two activities in this fraction that acetylate the peptide. A mutation, hat1-1, that eliminates one of the activities was identifie d and mapped to a locus near the centromere of chromosome XVI. The HAT 1 gene was cloned and found to encode a protein of 374 amino acids. An alysis of the peptide used in the assay demonstrated that the HAT1 enz yme acetylates lysine 12 of histone H4. hat1 mutants have no obvious g rowth defects or phenotypes other than the enzyme defect itself. The H AT1 protein expressed in Escherichia coil gave histone acetyltransfera se activity in vitro, demonstrating that HAT1 is the structural gene f or the enzyme.