Project description
The role of epigenetics in development
Early on during development, three layers of embryonic cells differentiate to give rise to the vertebrate body. The implicated events are driven by changes in gene expression, but the role of the epigenome remains poorly understood. The EU-funded EpiCellLineage project is working under the hypothesis that lineage-specific genes are epigenetically primed at early developmental stages to ensure transcription. Researchers will investigate the underlying molecular mechanisms and impact of impaired epigenetic priming. The project's results will unveil how the epigenetic landscape impacts cell differentiation during development, shedding light on developmental disorders.
Objective
Formation of the three primary germ layers during gastrulation is an essential step in the establishment of the vertebrate body plan. Single cell RNA-sequencing has identified major transcriptional changes associated with germ layer specification. Global epigenetic reprogramming accompanies these changes, but the role of the epigenome in regulating early cell fate choice is poorly understood. We are systematically charting this important developmental progression by single cell multi-omics, tracking simultaneously the transcriptome, DNA methylome and chromatin accessibility. We find that promoters or enhancers of lineage specific genes are epigenetically primed at early developmental stages to safeguard their future transcriptional activation. We have identified DNA binding proteins needed for multi-lineage priming of regulatory elements prior to gastrulation. Here, we will determine the molecular mechanisms of epigenetic priming, and the functional consequences of faulty priming in lineage and organ development. The first objective addresses how the DNA binding proteins DPPA2,4 target chromatin bivalency (H3K4me3 and H3K27me3) to developmental gene promoters, and the consequences of bivalency loss in vivo. The second objective characterises neuroectoderm enhancer priming which occurs already in the early epiblast, and identifies DNA binding proteins and chromatin complexes which prime these enhancers, preparing them for future gene activation. The third objective uses large-scale combinatorial epigenetic editing of promoters and enhancers in vitro and in vivo to determine their impact on cell fate decisions in gastrulation and early organogenesis. This ambitious programme of work will provide fundamental insights into how the epigenetic landscape in early development impacts cell differentiation. Our discoveries will inform strategies for ES or iPS cell based regenerative medicine, and improve our understanding of how developmental disorders arise in humans.
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
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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.1.1. - EXCELLENT SCIENCE - European Research Council (ERC)
MAIN PROGRAMME
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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.
ERC-ADG - Advanced Grant
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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) ERC-2019-ADG
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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.
CB22 3AT Cambridge
United Kingdom
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.