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DynaMech

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Linking Transcription Factor Binding Dynamics to Promoter Output

"Transcription is a stepwise process that is inherently dynamic. Different types of transcription factors are continuously interacting off and onto DNA, ""searching"" for appropriate interactions - each bringing different function... ver más

31/01/2021

PrinsesMaximaCentr...

2M€

Presupuesto del proyecto: 2M€

Líder del proyecto

PRINSES MAXIMA CENTRUM VOOR KINDERONCOLOGIE B... No se ha especificado una descripción o un objeto social para esta compañía.

TRL 4-5

Fecha límite participación Sin fecha límite de participación.

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Financiación concedida El organismo H2020 notifico la concesión del proyecto el día 2021-01-31

ERC-ADG-2014: ERC Advanced Grant

I+D

Cerrada hace 10 años

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2 Participantes

PrinsesMaximaCentrumvoorKind...

2.13M€ | Lider

LABORATORIO REIG JOFRE

3.01M€ | Participante

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Duración del proyecto: 62 meses Fecha Inicio: 2015-11-18
Fecha Fin: 2021-01-31

Líder del proyecto

PRINSES MAXIMA CENTRUM VOOR KINDERONCOLOGIE B... No se ha especificado una descripción o un objeto social para esta compañía.

TRL 4-5

Presupuesto del proyecto 2M€

Fecha límite de participación Sin fecha límite de participación.

Descripción del proyecto "Transcription is a stepwise process that is inherently dynamic. Different types of transcription factors are continuously interacting off and onto DNA, ""searching"" for appropriate interactions - each bringing different functions into play. The rates with which these factors interact with chromatin, their association and dissociation rates, dictate the outcome of ""steady-state"", developmental and rapidly responsive regulatory programs. Given the central role of transcription factors in biology and disease, it is remarkable that we know next to nothing about the dynamics of transcription factor-chromatin interactions. The objective of DynaMech is to implement technologies that will allow us to measure transcription factor binding dynamics (on- and off-rates) genome-wide, at binding site resolution. This will be applied to gain a systematic understanding of how these dynamics effect the function of transcription factors. Analyses will encompass components of the RNA polymerase II pre-initiation complex in yeast, as well as a comprehensive set of gene-specific transcription factors. For each of these factors we will determine the on- and off-rates genome-wide as well as the degree to which the mRNA synthesis rates from all promoters are dependent on the factor. This data will all be analysed in the context of nucleosome binding dynamics to understand the general principles of how chromatin-transcripton factor binding dynamics shape regulatory mechanisms. Through modelling promoter output and by additional perturbations, these principles will be explored to understand which properties of regulatory DNA determine differential transcription factor dynamics thereby causing differential promoter behaviour. We are as yet far from predicting regulatory outcome from regulatory sequence. The long-term aim of this work is to bring this closer, by bringing into play the almost completely unexplored aspect of transcription factor-chromatin interaction dynamics. "

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