Beyond the double helix: writing and reading the histone code

Abstract

Chromatin is the physiological carrier of not only genetic information, encoded in the DNA, but also of epigenetic information including DNA methylation and histone modifications. As such histone modifications are involved in many aspects of nuclear processes including gene regulation and chromosome segregation. Recently, a 'histone code' hypothesis was put forward to explain how patterns of histone modification may function in downstream processes. In support of the 'histone code' hypothesis, we found in vivo and in vitro evidence that effector proteins, HP1 (heterochromatin protein 1) and Pc (Polycomb) can discriminate and 'read' histone methylation marks on K9 and K27, respectively. Moreover, we propose a 'binary switch' model and suggest that binding and release of effector proteins to their cognate sites can be regulated by modifications on adjacent or nearby residues. Thus, combinations of adjacent histone modifications would function differently from singular modification, and static modifications (e.g. Lys methylation) may well be regulated by dynamic modifications (e.g. phosphorylation). Finally, we describe a novel histone phosphorylation event linking the function of Mst1 kinase and H2B Ser14 phosphorylation with apoptotic chromatin condensation in vertebrates. As this modification is not found during mitotic chromosome condensation, these findings suggest the intriguing possibility that a unique 'death' mark exists for chromatin condensation during apoptosis.