TimedEnhancer
Financiado
Temporal dependence of enhancer function
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 g...
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.
ver más
Duración del proyecto: 59 meses
Fecha Inicio: 2024-06-01
Fecha Fin: 2029-05-31
Fecha Fin: 2029-05-31
Línea de financiación: concedida
El organismo HORIZON EUROPE notifico la concesión del proyecto el día 2024-06-01
Línea de financiación objetivo
El proyecto se financió a través de la siguiente ayuda:
ERC-2023-STG:
ERC STARTING GRANTS
Cerrada
hace 2 años
Presupuesto
El presupuesto total del proyecto asciende a
2M€
Líder del proyecto
DEUTSCHES KREBSFORSCHUNGSZENTRUM HEIDELBERG
No se ha especificado una descripción o un objeto social para esta compañía.
Perfil tecnológico
TRL
4-5
Perfil tecnológico
TRL
4-5