Histone acetylase from Drosophila melanogaster specific for H4.

Abstract

Histone acetylation is a rapid and reversible modification which introduces significant changes in histone-DNA interactions. Such changes have been correlated with different states of DNA transcription and replication in the cell. We have purified a histone acetylase about 1200-fold from extracts of Drosophila melanogaster embryos. Major steps in the purification include chromatography on histone-Sepharose and Bio-Rex 70. This enzyme, the only histone acetylase detected in these extracts, acetylates only histone H4. All of the acetate groups are introduced within the NH2-terminal amino acids 4 to 17. This 14-residue peptide contains the four lysines which are acetylated in vivo. The acetylase is inhibited by its substrate, histone H4, and by several highly charged polymers including polylysine, polyarginine, DNA, RNA, and polyglutamic acid. It is not inhibited by polyethyleneimine, spermine, or the other histones H2A, H2B, H3, or H1. The enzyme does not acetylate H4 which is in chromatin. This enzyme is most likely involved in the acetylation of newly synthesized histones in the cytoplasm prior to chromatin assembly.