CE12 - Génétique, génomique et ARN

Uncovering the mechanisms & dynamics of proximity-dependent interallelic interactions – InterAlleles

Submission summary

The control of gene expression relies on cis-regulatory sequences. In many cases, however, proper regulation also requires interactions between homologous alleles. The mechanisms underlying this form of gene regulation, named transvection, are poorly understood. Transvection requires a close proximity for alleles to functionally interact. However, knowledge is scarse about the physical distances at which homologous alleles can functionally interact, about the time-dependence of their interaction, and about the consequences of the resulting dynamics on gene regulation. Answers to these questions will provide entry points for direct quantitative tests of the functional relationship between gene regulation and the spatial organization of the genome, in particular of homologous chromosomes in the nucleus. We will address these open questions by studying Drosophila genes whose regulation is influenced by transvection. Our ultimate goal is to define the distance-to-function relationship of interallelic interactions, quantitatively. For this, (aim 1) we will determine the physical proximity necessary for homologous alleles to functionally interact and the dynamics aspects of that interaction impacting transvection. Also, (aim 2) we will identify the molecular mechanisms underlying transvection via genetic perturbation experiments. To accomplish this work program, we will rely on powerful genetic tools available in Drosophila and on quantitative imaging of transcription and interallelic distances in both fixed and living tissues. The originality of the proposal stems from the quantitative methods we will apply to revisit an old problem: the simultaneous measurements of interallelic physical distance and gene expression at cellular resolution. Our ability to perturb the experimental systems in several independent ways and measure the consequences on interallelic distance and gene expression will lead to novel mechanistic and functional insights.

Project coordinator

Monsieur Benjamin PRUD'HOMME (Centre National de la Recherche Scientifique délégation Provence et Corse_Institut de Biologie du Développement de Marseille)

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

IP Institut Pasteur
CNRS DR12_IBDM Centre National de la Recherche Scientifique délégation Provence et Corse_Institut de Biologie du Développement de Marseille

Help of the ANR 532,121 euros
Beginning and duration of the scientific project: March 2023 - 48 Months

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