Nonstandard abbreviations used: histone acetyltransferase (HAT); histone deacetylase (HDAC); histone methyltransferase (HMT). importantly, these observations also raised the possibility that tail modifications not only contribute to the ongoing up-and downregulation of transcription but also carry information regarding the potential for transcription (or lack of it) in response to specific factors. In other words, the nucleosome may have a role not only in DNA packaging, but also in the transmission from one cell generation to the next of epigenetic information regarding transcriptional potential (8, 9). The amount of epigenetic information that can be carried in the histone tails is remarkable. For example, there are 50 different acetylated isoforms of the four core histones (H2B, H3, and H4 have 16 each and H2A has two). These isoforms can be modified further by methylation of selected lysines and arginines (H3 and H4) and phosphorylation of serine (H3, H4, H2B). Further, methylation can involve attachment of one, two, or three methyl groups (see below), and there are other modifications, such as ubiquitination and ADP-ribosylation (10). The total number of possible histone isoforms, carrying different combinations of tail modifications, that can mark the nucleosome surface, runs into many thousands. This has given rise to the idea that the tail modifications constitute a histone code (11, 12) or epigenetic code (13), which is set and maintained by tail-modifying and-demodifying enzymes and read by nonhistone proteins. The histone tail modifications are likely to act in concert with a rather more widely known mediator of chromatin structure and gene expression, namely methylation of cytosine residues in CpG dimers through the action of DNA methyltransferases. Long-term silencing, as found in imprinted genes or the female inactive X chromosome, is generally associated with relatively high levels of CpG methylation. The mechanism (s) by which CpG methylation leads to gene silencing remains to be defined, but there is evidence that in at least some situations, histone modifications are involved. The methyl DNA-binding protein MeCP2 can bind histone deacetylases, thereby targeting them to methylated DNA and resulting in local histone deacetylation and suppression of transcription (14). Conversely, experiments in the filamentous fungus Neurospora crassa have shown that DNA methylation is dependent upon methylation of histone H3 lysine 9 (15).