Skip to main content
Go to the home page of the European Commission (opens in new window)
English English
CORDIS - EU research results
CORDIS

Unravelling the impact of nucleosome arrays on condensin by implementing an in-vitro chromatin-loop extrusion assay

Project description

Molecular players of chromosome structure

Inside our cells, DNA is tightly coiled around proteins called histones, forming long strands known as chromatin fibres. These fibres are believed to fold further into loops, eventually creating the familiar X-shaped chromosomes seen during cell division. How this intricate 3D structure is organised is key to gene regulation, DNA damage repair and chromosome segregation. Supported by the Marie Skłodowska-Curie Actions programme, the ConNuc project studies condensin, a protein complex that drives the folding of chromatin loops and whose dysfunction is associated with various diseases. Researchers aim to uncover how this complex gains access to DNA packaged within nucleosomes, providing fundamental insights into genome organisation and its implications for health and disease.

Objective

The three-dimensional organization of chromosomal DNA is essential for critical genomic functions, including chromosome segregation, gene expression, and DNA damage repair. Structural Maintenance of Chromosomes (SMC) complexes, such as cohesin, the Smc5/6 complex, and condensin, are integral to preserving chromosomal architecture and supporting these vital processes. Condensin folds DNA into mitotic chromosomes through DNA loop extrusion, a process critical for proper chromosome segregation. Recent single-molecule studies using naked DNA as template have shed light on how condensin drives DNA loop extrusion through multiple dynamic DNA-protein contacts. However, in cells, DNA is organized into nucleosomes that further compact into chromatin fibers, stabilized by linker histone H1, which restricts DNA accessibility to most DNA-binding proteins. How condensin gets access to DNA and extrudes DNA wrapped into nucleosome arrays remains unclear. Understanding how condensin operates on chromatin fibers is essential, as dysregulation of condensin activity in humans is linked to neurological disorders, cancer, and Alzheimer’s disease. This research aims to explore whether and how condensin extrudes nucleosome arrays by implementing a novel single-molecule chromatin loop extrusion assay. This project aims to (1) examine whether in-vitro-reconstituted densely packed nucleosome arrays affect condensin-mediated DNA loop extrusion; (2) study the impact of internucleosomal linker DNA length on this process; (3) assess the influence of nucleosome compaction by linker histone H1 on condensin-mediated loop extrusion; (4) investigate the enhancement of condensin-mediated DNA loop extrusion by chromatin remodellers. Insights gained from these studies have the potential to significantly advance our understanding of how the condensin complex interacts with chromatin fibers and extrudes these fibers into loops within the cellular environment.

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.

You need to log in or register to use this function

Keywords

Project’s keywords as indicated by the project coordinator. Not to be confused with the EuroSciVoc taxonomy (Fields of science)

Programme(s)

Multi-annual funding programmes that define the EU’s priorities for research and innovation.

Topic(s)

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.

Funding Scheme

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.

HORIZON-TMA-MSCA-PF-EF - HORIZON TMA MSCA Postdoctoral Fellowships - European Fellowships

See all projects funded under this funding scheme

Call for proposal

Procedure for inviting applicants to submit project proposals, with the aim of receiving EU funding.

(opens in new window) HORIZON-MSCA-2024-PF-01

See all projects funded under this call

Coordinator

JULIUS-MAXIMILIANS-UNIVERSITAT WURZBURG
Net EU contribution

Net EU financial contribution. The sum of money that the participant receives, deducted by the EU contribution to its linked third party. It considers the distribution of the EU financial contribution between direct beneficiaries of the project and other types of participants, like third-party participants.

€ 217 965,12
Address
SANDERRING 2
97070 Wuerzburg
Germany

See on map

Region
Bayern Unterfranken Würzburg, Kreisfreie Stadt
Activity type
Higher or Secondary Education Establishments
Links
Total cost

The total costs incurred by this organisation to participate in the project, including direct and indirect costs. This amount is a subset of the overall project budget.

No data
My booklet 0 0