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From birth to action: regulation of gene expression through transcription complex biogenesis

Objetivo

Transcriptional regulation of protein coding genes in eukaryotic cells requires a complex interplay of sequence-specific DNA-binding factors, co-activators, general transcription factors (GTFs), RNA polymerase II and the epigenetic status of target sequences. Nuclear transcription complexes function as large multiprotein assemblies and are often composed of functional modules. The regulated decision-making that exists in cells governing the assembly and the allocation of factors to different transcription complexes to regulate distinct gene expression pathways is not yet understood. To tackle this fundamental question, we will systematically analyse the regulated biogenesis of transcription complexes from their sites of translation in the cytoplasm, through their assembly intermediates and nuclear import, to their site of action in the nucleus. The project will have four main Aims to decipher the biogenesis of transcription complexes:
I) Investigate their co-translation-driven assembly
II) Determine their cytoplasmic intermediates and factors required for their assembly pathways
III) Uncover their nuclear import
IV) Understand at the single molecule level their nuclear assembly, dynamics and action at target genes
To carry out these aims we propose a combination of multidisciplinary and cutting edge approaches, out of which some of them will be high-risk taking, while others will utilize methods routinely run by the group. The project builds on several complementary expertise and knowledge either already existing in the group or that will be implemented during the project. At the end of the proposed project we will obtain novel results extensively describing the different steps of the regulatory mechanisms that control the assembly and the consequent gene regulatory function of transcription complexes. Thus, we anticipate that the results of our research will have a major impact on the field and will lead to a new paradigm for contemporary metazoan transcription.

Convocatoria de propuestas

ERC-2013-ADG
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Régimen de financiación

ERC-AG - ERC Advanced Grant

Institución de acogida

CENTRE EUROPEEN DE RECHERCHE EN BIOLOGIE ET MEDECINE
Aportación de la UE
€ 2 500 000,00
Dirección
Rue Laurent Fries 1
67404 Illkirch Graffenstaden
Francia

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Región
Grand Est Alsace Bas-Rhin
Tipo de actividad
Research Organisations
Investigador principal
Laszlo Tora (Dr.)
Contacto administrativo
Steve Brooks (Dr.)
Enlaces
Coste total
Sin datos

Beneficiarios (1)