Gene expression regulation by cohesin

My PhD project investigates how the cohesin complex regulates gene expression through 3D genome organization, using C. elegans as a model organism. Cohesin mediates chromatin loop extrusion, influencing enhancer-promoter contacts critical for gene regulation. The project focuses on “fountain” structures—small chromatin domains enriched at active enhancers—and how their loss impacts gene expression following targeted cohesin (COH-1) cleavage.

To dissect these mechanisms at single-cell resolution, the project will combine bulk and single-nucleus multiomics (scRNA-seq and ATAC-seq), HiChIP, and the development of a single-cell Hi-TrAC protocol. This approach will map changes in enhancer occupancy, chromatin accessibility, and contact rewiring after cohesin removal. Particular attention is given to neuronal genes, due to their upregulation and behavioral relevance in cohesin-deficient animals—paralleling findings in Cornelia de Lange Syndrome.

By integrating transcriptomic, epigenomic, and chromatin conformation data, the project aims to clarify the regulatory roles of cohesin-mediated enhancer-promoter loops, identify affected neuronal subtypes, and highlight potential therapeutic targets for cohesinopathies.