CE12 - Génétique, génomique et ARN

Role of G-quadruplexes in transcription regulation – G4Access

Submission summary

G-quadruplexes (G4s) are secondary DNA structures alternative to the Watson-Crick double helix, extremely stable and well characterized in vitro. Until recently, their role in transcription has remained obscure due to conflicting results. Based on a robust set of preliminary data and the development of a novel technology, we propose a working model in which G4s act as promoter element and chromatin organizers. Our model more specifically proposes that G4s are essential to chromatin opening via nucleosome exclusion, which would constitute an essential, although not necessarily sufficient, step towards transcriptional activation.

Our project aims at fully demonstrating our hypothesis by deploying the following objectives: (1) mapping G4s associated to open chromatin, using a novel approach called G4access, in cellular models allowing large identification of SNPs associated to G4 potential, (2) studying their role in transcription through mutagenesis of promoters in genomic context and drug treatment, (3) inferring their structure on a large set of sequences and put it in relation to their genomic location and (4) demonstrating that G4s are essential promoter elements and dissect their sequence contribution in mammalian cells by developing a high-throughput integrative promoter assay.

Overall, our working model challenges the dominant ideas in the field by proposing that structural elements rather than specific sequence motifs are essential to define the intrinsic nature of a promoter. It thus carries the potential for a paradigm shift as well as proposing the development of new technologies that will contribute to the understanding of gene expression.

Project coordination

Jean-Louis MERGNY (Laboratoire d'Optique et Biosciences)

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

TAGC Théories et approches de la complexité génomique
LOB Laboratoire d'Optique et Biosciences
IGMM Institut de génétique moléculaire de Montpellier

Help of the ANR 524,856 euros
Beginning and duration of the scientific project: January 2021 - 36 Months

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