Correlation between butyrate-induced histone hyperacetylation turn-over and c-myc expression.

Transcriptionally active chromatin has an high level of histone acetylation, a post-transcriptional modification known to alter nucleosomal conformation increasing the accessibility of transcription factors to DNA. Recent studies have led new interest in histone acetylase and deacetylase because of their role as transcription factors. Sodium butyrate, a known reversible inhibitor of histone deacetylase, modulates a large number of genes. This report is focused on the modulation of the c-myc oncogene expression by butyrate. In HeLa cells, treated with butyrate and then exposed to butyrate-free medium, we established a correlation between the reactivation kinetic of c-myc expression and the increase in level of histone H4 acetylation. Both parameters, in cells exposed to butyrate-free medium, after showing a rebound effect, return to the control level. This trend was confirmed by quantitative analysis of the level of histone acetylation and of c-myc expression in the three distinct class of nucleosomal fragments with different transcriptional activity. In this chase process, we also detected a concomitant enrichment in c-myc sequences in the "active" chromatin fractions and decreased presence in the inactive nucleosomal fragment. Therefore we here demonstrate an excellent correlation between histone hyperacetylation and reactivation of a specific gene (c-myc).