Objective
A Locus Control Region can act in cis, regulating the expression of cytokine genes on the same chromosome but can also act in trans to regulate the expression of several cytokine genes located on different chromosomes. We have recently shown that the physical interchromosomal association of loci located on three different mouse chromosomes precedes differentiation of CD4+ T cells and acts as a checkpoint for T cell fate determination. The functional significance of these interchromosomal associations is under investigation and preliminary results point towards a repressive role in non-differentiated naïve CD4+ cells and an activatory role in differentiated T cells. As a next step, to further understand how these interactions are established, I propose to use genetic and biochemical approaches to isolate, purify and characterize the protein complexes that generate and maintain such interchromosomal interactions. The model I currently envision integrates cell and tissue specific transcription factors that recruit more general protein complexes with the potency to relocalize whole loci or chromosomes. Biocomputing analysis will be performed to identify the conserved elements on the interacting loci, located on three different mouse chromosomes, which will subsequently be used as baits to perform yeast one hybrid screens, as well as for direct isolation of proteins using biotinylated DNA probes. The protein complexes will then be tested for their ability to remodel or relocalize chromatin using a combination of techniques such as RNA and DNA fluorescence in situ hybridization (FISH) and chromosome conformation capture assays (3C) in wild type T cells as well as in cells with the identified respective genes knocked down, applying RNA-interference or knockout methodologies. The proposed project will provide substantial novel information on how the genome is shaped and how the nuclear structure affects global gene expression.
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 DNA
- natural sciences biological sciences biochemistry biomolecules proteins
- natural sciences biological sciences genetics RNA
- natural sciences biological sciences genetics chromosomes
- 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.
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.
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.
FP7-PEOPLE-IRG-2008
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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.
Coordinator
700 13 IRAKLEIO
Greece
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.