Histones: should I stay or should I go?

This year's American Society for Biochemistry and Molecular Biology symposium on transcription covered a wide variety of topics ranging from chromatin regulation, through the initiation of transcription and elongation process during transcription by RNA polymerase II (Pol II) to the roles of signaling in transcription and development. This report focuses on the sessions on chromatin, which led to many insightful discussions as a consequence of the rapid advances in this field over the past few years.A central role for chromatin in regulating processes such as transcription and replication is now widely recognized. It is generally believed that the dynamic regulation of chromatin structure makes use of a diverse repertoire of post-translational histone modifications, ATP-dependent chromatin remodeling and histone-variant exchange. Prevailing views on histone modification and its consequences for the modulation of chromatin dynamics, as proposed in the 'histone code hypothesis', suggest that combinations of covalent modifications of specific histone residues comprise a structural and chemical 'code' that can be recognized by other protein modules which then regulate DNA accessibility and function.Tony Kouzarides (University of Cambridge, UK) presented an interesting case that strongly supports this hypothesis. His group has found that methylation of lysine 20 of histone H4 in the fission yeast Schizosaccharomyces pombe is mediated by a novel protein, Set9, that contains a SET domain, a feature that characterizes a subset of chromatin modulators. Unlike other cases of histone lysine methylation, H4 Lys20 methylation appears not to be involved in regulating transcription or the formation of heterochromatin. Instead, it plays a pivotal role in the DNA-damage response pathway. Loss-of-function Set9 mutants and histone H4 K20R (lysine to arginine) mutants prematurely proceed to mitosis by skipping through the checkpoint that can cause arrest between G2 and M phases, even i