Histone H3 variants and partners in the nucleus

Chromatin organization in the nucleus of each cell provides a dynamic repertoire of information, beyond that encoded genetically. How the regulation of this organization contributes to genome function and stability with impact on cell fate is a major challenge (1). More specifically we have been interested in how chromatin organization is established, propagated, maintained, and altered during normal development and in response to environmental cues. Errors in the generation and inheritance of chromatin states can dysregulate essential genome functions associated with various pathologies including cancer. We have considered both the level of nucleosome formation with the choice of histone variants and the scale of higher-order organization in the nucleus with key chromosomal landmarks including gene loci, heterochromatin, centromeres and telomeres. Our working hypothesis has been that histone chaperones function in an ‘assembly line’ with specificity for individual histone variants to mark defined regions of the genome (2).