Description du projet
Comment les paysages régulateurs 3D façonnent-ils l’évolution de la détermination du sexe?
Toutes les cellules d’un organisme vivant héritent d’un génome complet, contenant un ensemble complet de gènes. Cependant, les cellules n’utiliseront que les gènes pertinents pour atteindre leur statut différencié et former les tissus associés. Le moment, l’endroit et la quantité d’expression des gènes sont contrôlés par des paysages régulateurs 3D, résultant d’une interaction entre les gènes, les éléments régulateurs et l’entreprise chromatinienne 3D. À ce jour, la façon dont les paysages régulateurs 3D influencent l’évolution des programmes de développement est encore extrêmement sous-explorée. Exploitant les récentes avancées technologiques, le projet 3D-REVOLUTION, financé par l’UE, étudiera cet aspect en utilisant comme modèle la détermination du sexe gonadique chez les tétrapodes.
Objectif
Vertebrate genomes are organized in 3D regulatory landscapes that control pleiotropic gene expression. Within them, transcription emerges from a precise interplay between genes, regulatory elements and 3D chromatin organization. We and others have shown how mutations in these regulatory layers can modulate phenotypes. However, how 3D regulatory landscapes shape the evolutionary history of developmental programs is still largely unexplored.
Our limited capability to read, interpret and modify genomes has constrained our knowledge on how gene regulation evolves. However, recent advances in long-range sequencing, single-cell, chromatin interaction and genome editing methods offer novel tools to link genomic variation and phenotypes. Here, I will combine these methods to investigate how changes in 3D regulatory landscapes contribute to refine the function of developmental programs. As a testbed, I will study gonadal sex determination, an essential process for species perpetuation but characterized by a remarkable evolutionary plasticity.
We will use single-cell transcriptomics across tetrapod clades to unravel the core and variable transcriptional network of sex determination. Single-cell epigenomics and novel chromatin interaction methods will reconstruct 3D regulatory landscapes and infer sources of regulatory variation. With phylogenomic comparative strategies, we will estimate the contribution of different types of mutations to different sex determination programmes, as well as the impact of whole genome duplications. Finally, we will develop innovative transgenic methods for inter-species replacement of 3D regulatory landscapes, using this technology to activate early estrogen synthesis in mouse.
3D-REVOLUTION will provide ground-breaking insights on the evolution of gene regulation. This will improve our understanding of the genomic sources and underlying mechanisms of phenotypical variation, which are relevant for developmental and evolutionary genetics.
Champ scientifique
Mots‑clés
Programme(s)
- HORIZON.1.1 - European Research Council (ERC) Main Programme
Régime de financement
HORIZON-ERC - HORIZON ERC GrantsInstitution d’accueil
28006 Madrid
Espagne