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Transcription factor binding as a function of chromatin

Objective

How the genomic blueprint of an organism is translated into cellular phenotype is a fundamental question in modern biology. The instructions need to be specifically regulated for cells to function. The regulation of the readout of this information is not entirely written in the DNA sequence but also requires epigenetic directives like DNA and histone modifications.
The maintenance of cellular states as well as their controlled differentiation requires the establishment of correct transcriptional patterns. Binding of specific transcription factors (TFs) to promoter and cis-regulatory regions is the key factor in regulating gene activity. This binding occurs in the context of chromatin, where nucleosomes and their modification states are thought to limit DNA access. This might in part account for why most TFs only occupy a minor fraction of their preferred sequence motifs. Moreover, chromatin sensitivity can create hierarchies between TFs since sensitive factors might rely on “pioneer” factors to establish a state of open chromatin. Despite its general relevance these models remain speculative due to limited understanding of the actual sensitivity of individual TFs to the local chromatin state.
To narrow this gap in our knowledge I will establish a system to locally manipulate chromatin in vivo and measure the resulting effect on binding of individual TFs at a defined chromosomal site. By systematic variation of nucleosome positioning and epigenetic modifications and its impact on TF occupancy this project aims to generate novel insight into the fundamental principles that regulate transcription output.

Fields of science (EuroSciVoc)

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Programme(s)

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Topic(s)

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Funding Scheme

Funding scheme (or “Type of Action”) inside a programme with common features. It specifies: the scope of what is funded; the reimbursement rate; specific evaluation criteria to qualify for funding; and the use of simplified forms of costs like lump sums.

MSCA-IF-EF-ST - Standard EF

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Call for proposal

Procedure for inviting applicants to submit project proposals, with the aim of receiving EU funding.

(opens in new window) H2020-MSCA-IF-2015

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Coordinator

FRIEDRICH MIESCHER INSTITUTE FOR BIOMEDICAL RESEARCH FONDATION
Net EU contribution

Net EU financial contribution. The sum of money that the participant receives, deducted by the EU contribution to its linked third party. It considers the distribution of the EU financial contribution between direct beneficiaries of the project and other types of participants, like third-party participants.

€ 175 419,60
Address
FABRIKSTRASSE 2
4056 BASEL
Switzerland

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Region
Schweiz/Suisse/Svizzera Nordwestschweiz Basel-Stadt
Activity type
Research Organisations
Links
Total cost

The total costs incurred by this organisation to participate in the project, including direct and indirect costs. This amount is a subset of the overall project budget.

€ 175 419,60
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