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DynaMech SIGNED

Linking Transcription Factor Binding Dynamics to Promoter Output

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EC-Contrib. €

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Project "DynaMech" data sheet

The following table provides information about the project.

Coordinator
PRINSES MAXIMA CENTRUM VOOR KINDERONCOLOGIE BV 

Organization address
address: HEIDELBERGLAAN 25
city: UTRECHT
postcode: 3584CS
website: www.prinsesmaximacentrum.nl

contact info
title: n.a.
name: n.a.
surname: n.a.
function: n.a.
email: n.a.
telephone: n.a.
fax: n.a.

 Coordinator Country Netherlands [NL]
 Total cost 2˙132˙500 €
 EC max contribution 2˙132˙500 € (100%)
 Programme 1. H2020-EU.1.1. (EXCELLENT SCIENCE - European Research Council (ERC))
 Code Call ERC-2014-ADG
 Funding Scheme ERC-ADG
 Starting year 2016
 Duration (year-month-day) from 2016-02-01   to  2021-01-31

 Partnership

Take a look of project's partnership.

# participants  country  role  EC contrib. [€] 
1    PRINSES MAXIMA CENTRUM VOOR KINDERONCOLOGIE BV NL (UTRECHT) coordinator 2˙132˙500.00

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 Project objective

'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. '

 Publications

year authors and title journal last update
List of publications.
2017 Wim J de Jonge, Eoghan O\'Duibhir, Philip Lijnzaad, Dik van Leenen, Marian JA Groot Koerkamp, Patrick Kemmeren, Frank CP Holstege
Molecular mechanisms that distinguish TFIID housekeeping from regulatable SAGA promoters
published pages: 274-290, ISSN: 0261-4189, DOI: 10.15252/embj.201695621
The EMBO Journal 36/3 2019-07-08

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