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Mechanisms of chromatin organization and reprogramming in totipotent mammalian zygotes

Objective

Totipotency, the developmental potential of a cell to give rise to all cell types, is naturally achieved when differentiated egg and sperm fuse to form the one-cell zygote. How chromatin is epigenetically reprogrammed to totipotency within hours after fertilisation remains a central question in biology. We aim to address this by investigating the mechanisms of reprogramming and the spatial reorganisation of chromatin in mammalian zygotes. Our interdisciplinary approach combines mechanistic cell biology with genetics and genomics to understand how chromatin reorganisation promotes totipotency and to identify key regulators of this process in zygotes. Molecular insights into reprogramming to totipotency are crucial to understand the essential zygotic stage of sexually reproducing species. A better understanding of how cells naturally reprogram chromatin to totipotency, a state upstream of pluripotency, has the potential to improve induced reprogramming technology and revolutionize regenerative medicine.

Our aim is to understand how chromatin is reprogrammed to totipotency. To reach this ambitious goal: 1) We will discover new general concepts of genome organization, as well as reprogramming-specific aspects, by capitalising on our recently developed single-nucleus Hi-C method to dissect spatial reorganisation of chromatin in zygotes. We will investigate the relationship between chromatin reorganisation and transcription. 2) We will uncover mechanisms of zygotic reprogramming by elucidating the loci and factors that support active DNA demethylation during reprogramming of the paternal genome. 3) We will illuminate the origins and contributions of the oocyte since the factors responsible for reprogramming likely reside as proteins or RNA in the unfertilized egg. Overall, these studies will provide novel insights into how chromatin is reprogrammed and spatially reorganised towards a totipotent state that facilitates zygotic genome activation.

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Keywords

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Programme(s)

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Topic(s)

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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.

ERC-COG - Consolidator Grant

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Call for proposal

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(opens in new window) ERC-2018-COG

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Host institution

MAX-PLANCK-GESELLSCHAFT ZUR FORDERUNG DER WISSENSCHAFTEN EV
Net EU contribution

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.

€ 1 555 255,00
Address
HOFGARTENSTRASSE 8
80539 MUNCHEN
Germany

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Region
Bayern Oberbayern München, Kreisfreie Stadt
Activity type
Research Organisations
Links
Total cost

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.

€ 1 555 255,00

Beneficiaries (2)

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