Chromatin organization in the nucleus of each cell provides a dynamic repertoire of information, beyond that encoded genetically. Regulation of this organization contributes to genome function and stability, with a major impact on cell fate. Our team investigates how chromatin organization is established, propagated, maintained, and altered during development and in response to environmental cues. Errors in the generation and inheritance of chromatin states can dysregulate essential genome functions, resulting in pathologies such as cancer.
Our objective is to decipher the mechanisms controlling chromatin dynamics, both at the level of nucleosome formation and at the scale of higher-order organization in the nucleus (Fig 1). We focus on challenges in physiological contexts such as replication, repair, cell cycle, development and cancer. Our hypothesis is that histone chaperones function in an ‘assembly line’ with specificity for individual histone variants to mark defined regions of the genome. Remarkably, we have found that misregulation of specific histone chaperones is a common feature of aggressive breast cancers. Our plan is to analyze the regulatory pathways that target histone chaperones and variants to control the assembly line and its connecting network. Our approach utilizes tools and model systems (e.g. Xenopus, mouse) that combine biochemistry, cell biology, developmental biology, epigenomics and advanced single molecule and single cell technologies.