HIPPOSTRUCT
Financiado
Structural insights into binding signatures of transcription factors regulated b...
Structural insights into binding signatures of transcription factors regulated by HIPPO signalling
Transcription factors (TFs) are proteins which recognize specific DNA-sequence to orchestrate various gene expression programs according to cellular requirements. Currently, approximately 1,600 TFs along with their binding motifs...
Transcription factors (TFs) are proteins which recognize specific DNA-sequence to orchestrate various gene expression programs according to cellular requirements. Currently, approximately 1,600 TFs along with their binding motifs have been annotated. Further, recent studies enabled classification of many of them according to their binding modes across nucleosome assembly. Despite such progress, interplay of different TFs in the context of adjacent DNA sequence or spatial organisation of chromatin is still largely unknown. This project aims to dissect crosstalk between different TFs that are targeted by HIPPO signalling pathway, a tumour suppressor pathway representing potential target for anti-tumour therapies. Preliminary data from host lab combined with previous studies from other groups lead us to postulate hypothesis that TFs from TEAD and FOX groups cooperate on regulation of transcription programs controlled by HIPPO pathway. Specifically, FOX TFs act as chromatin re-modellers enabling TEADs binding to the naked part of DNA which then triggers desired gene expression programs. To test this hypothesis, we will combine bioinformatic searches across human genome with experimental work assessing intermolecular binding between TFs and DNA, followed by structural characterization of selected macromolecular complexes. We will identify genomic loci which contains binding motifs for both TEAD and FOX TFs. These DNA fragment will be tested experimentally in terms of their ability to physically interact with both TFs, which will provide mechanistic insight into their cooperation. Finally, 3-D structure of the reconstituted complexes containing TF pairs bound to DNA will be determined using advanced mass spectrometry combined with high-resolution structural techniques such as X-ray crystallography and cryo-electron microscopy. This project will provide insight how TFs cooperate in the relevant genomic context with physiological chromatin architecture.
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Duración del proyecto: 25 meses
Fecha Inicio: 2020-04-15
Fecha Fin: 2022-05-31
Fecha Fin: 2022-05-31
Línea de financiación: concedida
El organismo H2020 notifico la concesión del proyecto el día 2022-05-31
Línea de financiación objetivo
El proyecto se financió a través de la siguiente ayuda:
WF-02-2019:
Widening Fellowships
Cerrada
hace 5 años
Presupuesto
El presupuesto total del proyecto asciende a
157K€
Líder del proyecto
MIKROBIOLOGICKY USTAV AV CR V.V.I
No se ha especificado una descripción o un objeto social para esta compañía.
Perfil tecnológico
TRL
4-5
Perfil tecnológico
TRL
4-5
584.75K€ |
Participante