Abstract

The control of cell identity entails a precise orchestration of gene expression programs. Although transcription factors play a crucial role in the establishment and maintenance of transcriptional networks, their action is constrained by chromatin. This nucleoproteic structure is tightly controlled by the combination of histone modifications, DNA methylation, histone variant deposition and nucleosome occupancy. The proper orchestration of these modifications requires a battery of enzymes, which precisely and dynamically regulate chromatin structure.

Recent whole-genome sequencing of large numbers of cancers has revealed that mutations of chromatin regulators is a recurrent theme across cancers yet it remains poorly understood how these mutations lead to the impairment of transcriptional programs. We are investigating this question in the context of the Polycomb machinery, a crucial actor for the maintenance of cell identity. I will present our studies aimed at understanding how the Polycomb machinery function, the consequences of its alterations and the therapeutic potential of modulating its activity.