Project description
Epigenetic reprogramming defines 3D chromatin structure and genome activation in the zygote
The totipotency of a single cell zygote that gives rise to all types of cells in an organism is a most intriguing subject in biology. The overall goal of the EU-funded Epigenome_embryo project is to understand the mechanisms of the establishment of the totipotent state. The generation of a zygote involves DNA demethylation of the paternal genome and asymmetry in histone modifications between the parental genomes. The study will examine whether and how epigenetic reprogramming modulates the 3D chromatin structure in zygotes. To study the zygotic genome activation (ZGA), the researchers will employ a targeted knockdown screen in embryos to identify the factors required for ZGA.
Objective
One of the most intriguing questions in biology is how a single cell (zygote) is generated that has the potential to give rise to all cell types of an organism, known as totipotency. The overall purpose of this project is to gain mechanistic insights into the establishment of the totipotent state, in terms of 3D chromatin organization and zygotic genome activation (ZGA), summarized in two key aims:
i)To test whether and how epigenetic reprogramming modulates the 3D chromatin structure in zygotes: The generation of a zygote is accompanied by Tet3-dependent active DNA demethylation of the paternal genome and asymmetry in histone modifications between the parental genomes. Whether this alters chromatin organization and promotes transcription is poorly understood. To test this, I will perturb Tet3 activity and perform single nucleus Hi-C (snHi-C) of zygotes to determine changes in genome architecture. In addition, I will study the effect of the absence of Kdm4a on the different histone marks and the consequent potential effect on chromatin architecture. This work will provide the first insights into how epigenetic reprogramming alters chromatin organization.
ii) To study the mechanism of ZGA: The activation of embryonic transcription is crucial for the development of an organism. However, the essential activators of ZGA in mammals remain largely unidentified. Based on work in Drosophila, a leading hypothesis is that ZGA is triggered by pioneer transcription factors. To identify these, I will participate in a targeted knockdown screen in embryos to identify factors required for ZGA. I will focus on one potential candidate and generate transgenic mouse strains to study its function in early embryos. This high-risk high-gain aim has the potential to identify novel regulators of the mammalian ZGA.
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 zoology mammalogy
- medical and health sciences clinical medicine embryology
- 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.
1030 Wien
Austria
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.