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Shedding light on three-dimensional gene regulation

Project description

Shedding light on 3D genome mysteries

Unlocking the secrets of gene expression hinges on our ability to understand the complex interplay within the three-dimensional (3D) chromatin structures of our genome. The mechanisms underlying these 3D chromatin interactions and their influence on gene expression remain elusive. The challenge lies in a lack of tools offering temporal control over regulatory proteins and high-resolution measurement of 3D chromatin interactions. With this in mind, the ERC-funded 3D-REG project aims to develop new tools to dissect the molecular mechanisms shaping our genome during cellular differentiation at high temporal and spatial resolution.

Objective

The orchestration of precise gene expression patterns during differentiation and development is dependent on the cis-regulatory elements of the genome, which interact and communicate in three-dimensional (3D) chromatin structures. It is not well understood how these interactions are formed and influence gene expression. Our ability to identify the molecular mechanisms involved is hampered by a lack of tools that provide control over the function of regulatory proteins with high temporal precision and that measure 3D chromatin interactions at high resolution. In this project, we will overcome these hurdles by utilizing an ultra-fast optogenetic system that allows for efficient and reversible nuclear depletion of mammalian proteins upon blue light exposure. We will combine this approach with a range of high-resolution genomic tools to investigate the context-specific functions of transcription factors, co-activators, and architectural proteins throughout erythroid differentiation. Importantly, our set-up does not only allow for characterisation of acute protein depletion, but also enables us to map the molecular events triggered by restoration of regulatory proteins to the nucleus. This unique approach will therefore provide detailed insight into their molecular functions. Moreover, to get a more complete overview of the proteins involved in gene activation, we will implement a locus-specific proteomics approach that enables unbiased identification of the proteome of regulatory regions. This innovative integrated research program has strong potential to transform our understanding of the molecular mechanisms that shape the genome and drive gene activation during cellular differentiation. Furthermore, it will lead to the development of cutting-edge tools to analyse gene regulation in its 3D context at high temporal and spatial resolution.

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Programme(s)

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Topic(s)

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HORIZON-ERC - HORIZON ERC Grants

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Call for proposal

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(opens in new window) ERC-2023-STG

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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.

€ 1 500 000,00
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.

€ 1 500 000,00

Beneficiaries (1)

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