The nucleosome core particle is the fundamental unit of chromatin structure in all eukaryotes. It comprises eight core histones (two each of H2A, H2B, H3, and H4) around which are wrapped 146 bp of DNA, and its structure has been defined at 2.8 Å resolution by x-ray crystallography (1). Since it was first described, it has been assumed that the function of the core particle is to package DNA into the interphase cell nucleus and metaphase chromosomes. Wrapping DNA around the histone octamer in left-handed supercoils results in an approximately sevenfold reduction in its length. Although this is only a small fraction of the several-thousand-fold length reduction required for compaction into metaphase chromosomes, it is presumably an essential first step that enables higher-order structures to assemble. The nucleosome’s rather mundane packaging job became more interesting with the realization that compaction of DNA into chromatin is a crucial element in eukaryotic gene regulation (2). Appropriately located nucleosomes can hinder assembly of transcription initiation complexes and polymerase progression, and over recent years, whole families of chromatin-remodeling enzymes have been identified whose primary purpose is to reorganize histone-DNA interactions so as to facilitate (or repress) transcription (3). These enzymes disrupt the nucleosome in an ATP-dependent manner that often results in movement of the histone core relative to the DNA, thereby exposing recognition sequences for DNA-binding activators or repressors. However, even these insights still left the nucleosome as a passive inhibitor of transcription, something to be moved aside so transcription could proceed. The final transformation of the nucleosome into a truly exciting and colorful character has come through studies on the effects and properties of other enzymes that act on chromatin. It has been known for many years that the histone N-terminal tails are exposed on the surface of the nucleosome and that selected amino acid residues are subject to a variety of enzyme-catalyzed, posttranslational modifications. These include acetylation of lysines, phosphorylation of serines, and methylation of lysines and arginines. The locations of the histone N-terminal tails in the nucleosome and the residues that can be modified are shown in Figure Figure1.1. The function of these modifications, and indeed of the tails themselves, is the focus of much current attention, centered largely on the possibility that the nucleosome, with its modified tail domains, is not just a humble packer of DNA, but a carrier of epigenetic information that determines both how genes are expressed and how their expression patterns are maintained from one cell generation to the next. Figure 1 A nucleosome core particle, showing the core histone N-terminal tail domains and sites of posttranslational modification. Residue numbers for modified residues are shown. Note that H3 lysine 9 (star) can be either acetylated or methylated. The C-terminal ...