Lack of correlation between histone H4 acetylation and transcription during the Physarum cell cycle

The interaction between nucleosomal proteins and DNA is expected to change during DNA replication as well as during transcription. A possible way of achieving the necessary structural changes is the modification of histones and high mobility group (HMG) proteins. The acetylation of core histones has been studied in various systems (for a review see ref. 1) and a correlation between histone acetylation and transcriptional activity of chromatin has frequently been proposed. In particular, Bradbury and co-workers have reported a cell cycle dependence of histone H4 acetylation in Physarum polycephalum which revealed two correlations: (1) tetraacetylated H4 (H4Ac4) correlated with the rate of transcription and (2) H4 acetylation was inversely correlated with H1 phosphorylation in mitosis. We present evidence here that H4 acetylation does not fit these correlations. Our data clearly show that the acetate content of H4 is high during the S phase, but low during later stages of the cell cycle. H4Ac4 remains at a nearly constant level during the whole cycle, with an elevation during the S phase. Furthermore, experiments with the deacetylase inhibitor sodium-n-butyrate do not support the proposed connection between diacetylated H4 (H4Ac2) and DNA replication. Our data imply that a correlation of H4 acetylation and transcription is unlikely during the cell cycle of Physarum. The conclusions of Bradbury and co-workers are therefore invalid.