Objective
The regulation of gene transcription by RNA polymerase (Pol) II underlies cell differentiation and organism development, and its dysregulation causes many cancers. Transcription regulation occurs during initiation, when Pol II assembles with initiation factors on promoter DNA, but also during mRNA chain elongation, when Pol II pauses near the promoter before it restarts upon activation. Our previous ERC Advanced Grant ‘TRANSIT’ enabled us to provide molecular insights into yeast Pol II initiation and its regulation by the Mediator coactivator complex (Plaschka et al., Nature 2015; Sainsbury et al., Nature 2012, Lariviere et al, Nature 2012). Here, with our new proposal ‘TRANSREGULON’ we wish to open a new frontier and provide the structural basis for mammalian Pol II regulation during elongation. We will use an integrated structural biology approach combining X-ray crystallography, cryo-electron microscopy, and crosslinking, to obtain the first atomic structure of a mammalian Pol II enzyme (aim 1), the structure of the negative elongation factor NELF (aim 2), which is required for promoter-proximal pausing by mammalian Pol II, and the threedimensional architecture of the promoter-proximally paused Pol II complex (aim 3) containing the multiprotein pausing factors NELF and DSIF, and eventually also the pause release factor p-TEFb. This ground-breaking work will make the transition from yeast to human structural biology of transcription, will provide the molecular basis for a central mechanism of cellular regulation, and will advance structural biology methods for dissecting large and transient mammalian multicomponent complexes.
Fields of science (EuroSciVoc)
CORDIS classifies projects with EuroSciVoc, a multilingual taxonomy of fields of science, through a semi-automatic process based on NLP techniques. See: https://op.europa.eu/en/web/eu-vocabularies/euroscivoc.
CORDIS classifies projects with EuroSciVoc, a multilingual taxonomy of fields of science, through a semi-automatic process based on NLP techniques. See: https://op.europa.eu/en/web/eu-vocabularies/euroscivoc.
- natural sciences earth and related environmental sciences geology mineralogy crystallography
- natural sciences physical sciences optics microscopy
- natural sciences biological sciences genetics RNA
- natural sciences biological sciences biochemistry biomolecules proteins enzymes
- natural sciences biological sciences molecular biology structural biology
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Programme(s)
Multi-annual funding programmes that define the EU’s priorities for research and innovation.
Multi-annual funding programmes that define the EU’s priorities for research and innovation.
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H2020-EU.1.1. - EXCELLENT SCIENCE - European Research Council (ERC)
MAIN PROGRAMME
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Topic(s)
Calls for proposals are divided into topics. A topic defines a specific subject or area for which applicants can submit proposals. The description of a topic comprises its specific scope and the expected impact of the funded project.
Calls for proposals are divided into topics. A topic defines a specific subject or area for which applicants can submit proposals. The description of a topic comprises its specific scope and the expected impact of the funded project.
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.
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.
ERC-ADG - Advanced Grant
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Call for proposal
Procedure for inviting applicants to submit project proposals, with the aim of receiving EU funding.
Procedure for inviting applicants to submit project proposals, with the aim of receiving EU funding.
(opens in new window) ERC-2015-AdG
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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.
80539 MUNCHEN
Germany
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.