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Temporal dependence of enhancer function

Objective

During vertebrate development, genes are regulated by distal regulatory elements, presumably via physical contacts between enhancers and transcription start sites. Alterations in enhancer sequences and/or their interactions with gene promoters can perturb gene expression, leading to developmental disorders and cancers, which argues for their pivotal role in transcription. Conversely, enhancer-promoter contacts can also be uncoupled from gene activation during developmental transitions and in single cells, where they are highly heterogeneous. Thus, the relationship between enhancer-promoter interactions and transcription is frequently indirect and the mechanisms that dictate when promoter-enhancer contacts can result in gene expression differences remain unknown. The core hypothesis of this proposal is that it is the timing of promoter-enhancer communication that instructs gene activation.

Aim1 will examine whether and how the precise timing of enhancer-promoter interactions contributes to transcription. My group will determine which molecular mechanisms during transcriptional activation are regulated by enhancers contacting their target genes at different time points during embryonic stem cell differentiation.

Aim2 will investigate how present and preceding enhancer-promoter contacts relate to transcriptional activity and transcription factor binding in single cells. My group will develop a genomic approach to trace the memory of preceding interactions at gene regulatory elements, thus adding a novel temporal dimension to current single-cell methods.

By longitudinally combining cutting-edge genomic, single-cell and activity perturbation assays, my group will uncover how genes integrate regulatory inputs from several enhancers and assess how the timing of genome folding mechanistically contributes to this process. This research plan will newly elucidate temporality as a powerful feature that shapes the regulatory potential of enhancers and promoters.

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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

DEUTSCHES KREBSFORSCHUNGSZENTRUM HEIDELBERG
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
IM NEUENHEIMER FELD 280
69120 Heidelberg
Germany

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Region
Baden-Württemberg Karlsruhe Heidelberg, Stadtkreis
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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