Nuclear pores and chromatin organization: a crosstalk?

Chromatin organization plays a crucial role in regulating DNA-related processes such as transcription, replication, and repair. In most somatic cells, heterochromatin localizes at the nuclear periphery while euchromatin is broadly distributed within the nucleus. This spatial organization is believed to mostly rely on the association of heterochromatin with the nuclear lamina, which in turn participates in gene repression. In a striking contrast, the nuclear pore vicinity is always devoid of heterochromatin, therefore forming heterochromatin exclusion zones within the heterochromatin layer of the nuclear periphery. In rupture with the classical view that the nuclear lamina stands as the main determinant of heterochromatin accumulation at the nuclear periphery, I propose that it rather results from an equilibrium between attraction at the nuclear lamina and exclusion from the adjacent nuclear compartment: the nuclear pores. I further propose that by excluding heterochromatin, nuclear pores participate in global chromatin organization, and thereby impact gene regulation. Whether the absence of heterochromatin at nuclear pores impacts their function is unknown. Using a combination of advanced microscopy techniques, proteomics and genomics, I will interrogate the crosstalk between nuclear pores and chromatin organization by addressing three fundamental questions: (1) What is the contribution of heterochromatin exclusion zones to global chromatin organization? (2) What are the mechanisms underlying heterochromatin exclusion zone maintenance at nuclear pores? (3) What is the role of heterochromatin exclusion in nuclear pores transport? The NCORe project therefore promises to shed light on new mechanisms regulating chromatin organization and nucleocytoplasmic transport.