CE12 - Génétique, génomique et ARN

Determinants of transcription regulation by co-activator complexes – COACTIVATOR

Submission summary

Transcription involves the coordinated activities of a multitude of regulatory factors. An important class of regulators has chromatin-modifying or –remodeling activities and function as co-activators during transcription initiation. Co-activators are typically multifunctional complexes that integrate regulatory information from promoter elements, transcription factors, and chromatin marks. Despite the advent of functional genomics, understanding how these factors establish specific gene expression programs remains challenging, likely because our view of their function is static. Here we propose a systems biology approach combining kinetic analyses, innovative transcriptomic approaches, and computational modelling to address this issue. We will measure the effects of co-activators on the temporal dynamics of transcription, nucleosome modifications, and general transcription factor assembly, allowing the ordering of mechanistic events. These data will be integrated into a stochastic biophysical model of transcription regulation by co-activators, which predictions will be tested experimentally. Overall, we expect to identify the principles governing the gene-specific effects of co-activators and to better understand how these properties sustain both robustness and plasticity of gene expression in response to perturbations.

Project coordination

Dominique HELMLINGER (Centre de Recherche en Biologie cellulaire de Montpellier)

The author of this summary is the project coordinator, who is responsible for the content of this summary. The ANR declines any responsibility as for its contents.

Partner

IGBMC Institut de génétique et de biologie moléculaire et cellulaire (UM 41 - UMR 7104 - UMR_S 1258)
CRBM Centre de Recherche en Biologie cellulaire de Montpellier
IGBMC Institut de génétique et de biologie moléculaire et cellulaire (UM 41 - UMR 7104 - UMR_S 1258)

Help of the ANR 575,749 euros
Beginning and duration of the scientific project: February 2021 - 48 Months

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