Unveiling ROSEE: Exploring Early X Chromosome Organization and Function in C. elegans

• Applicant: Fanny Eggeler, Ph.D.
• Subject Area: Developmental Biology
• Term: since 2025
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 562968357

Over the past fifteen years, studies have illuminated the 3D conformations of chromosomes, yet their functional significance remains unclear across various animal systems. Dosage compensation (DC), a well-studied example of chromosome-wide organization, equalizes X chromosome expression between sexes. This project investigates a novel X chromosome structure in C. elegans, termed ROSEE (ROSette in Early Embryos), observed in early embryogenesis before DC onset. ROSEE consists of looped chromatin ("Petals") connected to compact domains ("Hubs") and appears in both sexes. This study hypothesizes that ROSEE represents a precursor to dosage-compensated X and aims to test its potential roles in facilitating DC and regulating gene expression. The first objective is to determine if ROSEE aids DC complex (DCC) loading, as its open Petal regions house key regulatory sites for DCC binding. Using CRISPR engineering, biochemical analyses, and the Cut&Tag technique, this study will explore whether Petals promote DCC recruitment compared to the compact Hubs. The second objective investigates ROSEE’s role in regulating gene expression in early embryos of both sexes and the parental germline. Preliminary data suggest that ROSEE represses X-linked gene expression, a hypothesis that will be tested using smFISH in wild-type and mutant strains. This project is innovative in its focus on a previously uncharacterized chromosomal structure and its use of advanced methodologies, including Chromosome Tracing to resolve 3D organization at a single-molecule resolution. By investigating ROSEE’s biological function, this research will provide key insights into the mechanisms of X chromosome regulation, the dynamics of large-scale chromosomal organization, and cross-generational signaling, advancing our understanding of genomic structure-function relationships.

• DFG Programme: WBP Fellowship
• International Connection: Switzerland
• Host: Professorin Dr. Susan Elizabeth Mango