Understanding the interplay between transcription and cohesin-mediated loop extrusion at the single molecule level

• Applicant: Eugene Kim, Ph.D.
• Subject Area: General Genetics and Functional Genome Biology ; Biophysics
• Term: since 2022
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 507934376

The spatial structure of the genome is tightly connected to its function. While it is known that the genome organization influences gene expression, the impact of transcription on the genome organization remains to be understood. The process of loop extrusion is central to chromosome organization. In eukaryotes, the cohesin complex extrudes large chromatin loops by translocating along arms of the chromosome. During translocation, cohesins encounter the transcription machinery, which could interfere with loop extrusion. In this proposal, we aim to investigate the interplay between these two important active processes and determine whether and how transcription can modulate loop extrusion and vice versa. To this end we will employ in vitro single molecule imaging for the visualization of loop extrusion mediated by cohesin. Of particular interest is whether the transcription machinery acts as a ‘moving barrier’ to loop extruding cohesin and how the directionality of transcription and the topological state of transcribed DNA interfere with the kinetics of loop extrusion. The prospective findings will provide a molecular basis for understanding the functional relation between gene expression and loop extrusion. In the long term this knowledge will be crucial for understanding how loop extrusion actively regulates gene expression and how transcriptional activity shapes functional genomic organization.

• DFG Programme: Priority Programmes
• Subproject of: SPP 2202: Spatial Genome Architecture in Development and Disease