Effects of histone acetylation on chromatin topology in vivo

Recently a model for eukaryotic transcriptional activation has been proposed in which histone hyperacetylation causes release of nucleosomal supercoils, and this unconstrained tension in turn stimulates transcription (V. G. Norton, B. S. Imai, P. Yau, and E. M. Bradbury, Cell 57:449-457, 1989; V. G. Norton, K. W. Marvin, P. Yau, and E. M. Bradbury, J. Biol. Chem. 265:19848-19852, 1990). These studies analyzed the effect of histone hyperacetylation on the change in topological linking number which occurs during nucleosome assembly in vitro. We have tested this model by determining the effect of histone hyperacetylation on the linking number change which occurs during assembly in vivo. We find that butyrate treatment of cells infected with simian virus 40 results in hyperacetylation of the histones of the extracted viral minichromosome as expected. However, the change in constrained supercoils of the minichromosome DNA is minimal, a result which is inconsistent with the proposed model. These results indicate that the proposed mechanism of transcriptional activation is unlikely to take place in the cell.