Histone exchange: sculpting the epigenome

Chromatin not only serves as a packaging material, but also functions as a platform for integrating signals that act upon the genome. Indeed, chromatin is a dynamic macromolecular structure that can be dramatically altered in many ways to facilitate the different transactions at the genome. Examples of such alterations are relocalization of genomic loci within the nucleus upon transcriptional activation or induction of DNA damage, adding or removing post-translational modifications on histones or other chromatin-binding factors, or altering the basic organization of chromatin by moving or removing nucleosomes, i.e. modifying the occupancy of histone octamers. New insights into the scope and mechanisms of chromatin dynamics have recently been obtained by the development of novel techniques to visualize chromatin protein mobility and stability. Here we discuss the developments in this area, with special emphasis on histone exchange, which we define as the replacement of histone proteins without a prerequisite change in occupancy. Although histone exchange may not affect chromatin organization per se, recent studies suggest that it can influence key epigenetic processes such as histone inheritance, the distribution of histone post-translational modifications, and the output of transcription factors. Importantly, errors in histone exchange in humans can contribute to malignant transformation.