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DynaMech SIGNED

Linking Transcription Factor Binding Dynamics to Promoter Output

Total Cost €

EC-Contrib. €

Partnership

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Outcomes and
results

DynaMech project word cloud

Explore the words cloud of the DynaMech project. It provides you a very rough idea of what is the project "DynaMech" about.

perturbations play understand central predicting completely dynamic association inherently rna systematic mechanisms analysed degree promoters dissociation resolution genome sequence initiation mrna regulatory synthesis nucleosome closer gain transcripton effect dictate principles transcription promoter function developmental gene onto appropriate context polymerase dynamics differential responsive nothing components biology data functions dna interaction unexplored rates interactions interact searching types yeast programs shape stepwise steady off binding interacting thereby almost dynamech outcome additional output technologies remarkable chromatin dependent explored causing disease site

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 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.	NL (UTRECHT)	coordinator	2˙132˙500.00

Map

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

List of publications.
year	authors and title	journal	last update
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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