Project description
Rethinking how the cell nucleus organises its genetic code
Inside every cell, DNA is carefully folded and arranged. It is a structure known as chromatin that determines which genes are active or silent. Traditionally, scientists believed that dense, inactive chromatin gathered along the nuclear lamina at the cell’s edge, while the nuclear pores, which are gateways controlling molecular traffic, simply acted as openings. The ERC-funded NCOre project aims to challenge this view. It proposes that nuclear pores actively shape chromatin organisation by creating zones that repel dense DNA. Using advanced microscopy, proteomics, and genomics, NCOre will explore how this balance between attraction and exclusion structures the genome, influences gene activity, and redefines our understanding of the cell’s inner architecture.
Objective
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.
Fields of science (EuroSciVoc)
CORDIS classifies projects with EuroSciVoc, a multilingual taxonomy of fields of science, through a semi-automatic process based on NLP techniques. See: The European Science Vocabulary.
CORDIS classifies projects with EuroSciVoc, a multilingual taxonomy of fields of science, through a semi-automatic process based on NLP techniques. See: The European Science Vocabulary.
- natural sciences biological sciences genetics
- natural sciences biological sciences biochemistry biomolecules proteins proteomics
- natural sciences physical sciences optics microscopy
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Project’s keywords as indicated by the project coordinator. Not to be confused with the EuroSciVoc taxonomy (Fields of science)
Project’s keywords as indicated by the project coordinator. Not to be confused with the EuroSciVoc taxonomy (Fields of science)
Programme(s)
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Multi-annual funding programmes that define the EU’s priorities for research and innovation.
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HORIZON.1.1 - European Research Council (ERC)
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Calls for proposals are divided into topics. A topic defines a specific subject or area for which applicants can submit proposals. The description of a topic comprises its specific scope and the expected impact of the funded project.
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Funding scheme (or “Type of Action”) inside a programme with common features. It specifies: the scope of what is funded; the reimbursement rate; specific evaluation criteria to qualify for funding; and the use of simplified forms of costs like lump sums.
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(opens in new window) ERC-2025-STG
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75794 PARIS
France
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