Project description
Cofactor mechanisms in transcription dynamics
Transcription is tightly regulated by cofactors that enhance its efficiency, yet their precise mechanisms remain unclear. The ERC-funded DYNACOF project will investigate how cofactors influence transcription by using advanced single-molecule imaging and perturbation experiments in living yeast cells. By analysing DNA-binding dynamics and transcriptional activity at the single-gene level, the project will uncover key steps in transcription regulation, including cooperativity and bursting properties under different cofactor perturbations. It will also examine the interactions between cofactors, transcription factors, and the pre-initiation complex to construct a kinetic model of transcription. The findings will provide a deeper understanding of how individual cofactor-binding events contribute to transcription activation.
Objective
Transcription is a multi-step process involving many regulatory factors, including cofactors such as Mediator, chromatin remodelers and chromatin modifiers. Cofactors are thought to enhance transcription efficiency, but a detailed mechanistic understanding of cofactor action is still lacking. Inside single cells, the transcriptional process is highly dynamic, with regulatory factors transiently associating to DNA, and transcription occurring in stochastic bursts of high transcriptional activity, interspersed by periods of inactivity. How cofactors regulate these dynamics is so far largely unexplored. In this proposal, we aim to elucidate the molecular mechanisms of cofactor action, by combining perturbation experiments with cutting-edge single-molecule imaging techniques to measure the DNA binding dynamics of regulatory factors (input) as well as the stochastic behavior of transcription (output) in living yeast cells. First, bursting properties will be quantified at endogenous genes upon single and double cofactor perturbations to identify rate-limiting steps that are regulated by cofactors and to determine cooperativity between cofactors. Second, the DNA binding dynamics of cofactors, transcription factors and the preinitiation complex will be determined in wildtype and upon perturbations of cooperating cofactors, allowing us to construct a kinetic model of transcription. Third, building on our recently developed imaging technique, we will develop a new technology to simultaneously visualize the DNA binding of single cofactor molecules and transcriptional output at a single target locus to dissect the functional effect of cofactor DNA binding events on transcription activation. Overall, our results will provide unique insight into the composition of and transitions between transcription regulatory steps, uncovering mechanisms how cofactors increase transcription efficiency.
Fields of science (EuroSciVoc)
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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.
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Project’s keywords as indicated by the project coordinator. Not to be confused with the EuroSciVoc taxonomy (Fields of science)
Programme(s)
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Multi-annual funding programmes that define the EU’s priorities for research and innovation.
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HORIZON.1.1 - European Research Council (ERC)
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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.
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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.
HORIZON-ERC - HORIZON ERC Grants
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Call for proposal
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(opens in new window) ERC-2024-COG
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1066 CX AMSTERDAM
Netherlands
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