DNA is organized into a hierarchy of structures, resulting in the level of compaction required to pack 2 m of DNA into a nucleus with a diameter of 10 mu m. The orderly packaging of DNA in the nucleus plays an important role in the functional aspects of gene regulation. A small percentage of chromatin is made available to transcription factors and the transcription machinery, while the remainder of the genome is in a state that is essentially invisible to the RNA polymerases. Modification of histones has a key role in altering chromatin higher order structure and function. In this review, we will present the latest developments in the study of histone modifications (ubiquitination, acetylation, methylation, and phosphorylation) and the enzymes involved in these processes. (C) 1999 Published by Elsevier Science B.V. All rights reserved.