Histones are DNA binding proteins that bind without regard to the sequence of the DNA and help determine the three-dimensional organization of the chromatin into chromosomes. A paper in this week's issue (Taunton et al ., p. 408 ) reports the cloning of histone deacetylase, an ezyme that modifies histones by removing an acetyl group. In his Perspective, Wolffe explains how the action of this enzyme can lead to the regulation of the transcription of certain genes.