Project description
The sequences that drive LAD formation
Lamina-associated domains (LADs) cover 40 % of the human genome and hold thousands of transcriptionally repressed genes. While LAD recognition and anchoring to the nuclear lamina (NL) need to be tightly regulated to ensure acute gene expression, little is known about the underlying mechanisms. LADs are known to be A and T nucleotide-rich but other sequence determinants are poorly characterised. The EU-funded I.am.a.LAD project will first examine how LAD recognition is linked to their A/T content. Second, through this Marie Skłodowska-Curie fellowship, the researcher will develop a tool to search for additional sequence determinants. Finally, the MSCA fellow will identify sequences that drive LAD formation and elucidate the role of the cohesin complex in this process.
Objective
"Lamina-associated domains (LADs) are large chromatin domains anchored to a protein meshwork coating the inner nuclear envelope, the nuclear lamina (NL). They cover 40% of the human genome and hold thousands of transcriptionally repressed genes. While some LADs can be locally detached from the NL upon gene activation, others are constitutively at the NL. This implies that LAD recognition and anchoring to the NL has to be tightly regulated to ensure acute gene expression. However, little is known about mechanisms governing LAD recognition and targeting to the NL. LADs are known to be A and T nucleotide-rich, but other sequence determinants have remained poorly characterized so far. In this project I will (1) investigate whether LAD recognition is directly linked to their high A/T content and (2) develop a novel tool to search for additional sequence determinants. First, I will insert in the mouse genome long DNA stretches of varying A/T percentages and determine whether A/T-rich sequences preferentially associate with the NL. Second, I will develop an approach to randomly scramble a LAD sequence organization. This method relies on the recombination between LoxP sites randomly inserted by local ""hopping"" of a transposable element. After determining the effects of the resulting rearrangements on NL association and expression of the surrounding genes, I will identify sequences that drive LAD formation. Besides, the cohesin complex partitions the genome into topologically associated domains and hence has a major impact in genome 3D folding. At last, I will investigate cohesin’s role in LAD formation and remodeling after recombination. Altogether, this project will result in an unprecedented characterization of LAD biology, a deeper understanding of cohesin’s role in genome folding and set up a novel genome-scrambling technique with large applications in genome biology."
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.
- engineering and technology materials engineering fibers
- natural sciences biological sciences genetics DNA
- natural sciences biological sciences biochemistry biomolecules proteins
- engineering and technology materials engineering coating and films
- natural sciences biological sciences genetics genomes
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Keywords
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)
Multi-annual funding programmes that define the EU’s priorities for research and innovation.
Multi-annual funding programmes that define the EU’s priorities for research and innovation.
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H2020-EU.1.3. - EXCELLENT SCIENCE - Marie Skłodowska-Curie Actions
MAIN PROGRAMME
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H2020-EU.1.3.2. - Nurturing excellence by means of cross-border and cross-sector mobility
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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.
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.
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.
MSCA-IF - Marie Skłodowska-Curie Individual Fellowships (IF)
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Call for proposal
Procedure for inviting applicants to submit project proposals, with the aim of receiving EU funding.
Procedure for inviting applicants to submit project proposals, with the aim of receiving EU funding.
(opens in new window) H2020-MSCA-IF-2020
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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.
1066 CX AMSTERDAM
Netherlands
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.