Project description
Decoding TF cooperativity in gene expression from the inactive X chromosome
The role of transcription factors (TFs) is to regulate gene expression at the right time and in the right amount throughout the life of the cell and the organism. During female mammalian development, one of the two X chromosomes is inactivated. However, a small fraction of genes of the inactivated X (Xi) chromosome are still expressing. The exact mechanisms regulating their expression and the coordination with the genes from the active X chromosome are unknown. The EU-funded TAXi-ch project aims to determine the TFs driving the expression of genes from the Xi chromosome. The research is innovative, as this question has not previously been addressed using an integration of allele-specific multi-omics data; furthermore, the results of the project will be important to the study of X-linked disorders.
Objective
Transcription factor (TF) cooperativity controls gene expression and is essential to establish transcriptional programs during development. One of the hallmarks of development in female mammals is the inactivation of one of the two X chromosomes to achieve dosage compensation of X-linked genes. Although the inactive X (Xi) chromosome is a heterochromatin environment, a small fraction of genes is expressed from this chromosome. However, the exact mechanisms regulating their expression and the possible similarities in regulation between these genes and genes from the active X chromosome are unknown. TAXi-ch aims to determine the TFs driving the expression of genes from the Xi chromosome, as well as, the contribution of each TF to this process and their cooperativity. Specifically, an interdisciplinary approach based on functional genomics techniques, machine learning algorithms and genome editing tools will be applied to: 1) predict TFs that bind regulatory regions in the X chromosomes and generate their binding profiles, 2) assess the contribution of TFs to gene expression through classification models and targeted depletion of TFs, 3) infer regulatory networks of X-linked genes in the Xi chromosome, 4) model the transcriptional effect of abolishing binding of different combinations of TFs using 2 selected networks, and 5) experimentally validate the modelling predictions. The research is innovative, as this question has not previously been addressed using integration of allele-specific multi-omics data, and timely, considering the current interest to understand TF cooperativity. Furthermore, the results of this project will be important to the study of X-linked disorders. The dual expertise on data analysis and molecular biology of the experienced researcher ensures the feasibility of the project, and its implementation will hone her technical and transferable skills to facilitate her future establishment as an independent leader in the European Research Area.
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 computer and information sciences data science
- natural sciences biological sciences zoology mammalogy
- natural sciences biological sciences genetics chromosomes
- natural sciences computer and information sciences artificial intelligence machine learning
- natural sciences biological sciences molecular biology
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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-2019
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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.
69117 Heidelberg
Germany
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.