Anders Hansen: Dynamics of 3D Genome Structure and Function

Nov 14, 2022, 12:30 pm1:30 pm
Joseph Henry Room, Jadwin Hall



Event Description

Animal genomes are folded into loops and topologically associating domains (TADs) by CTCF and loop extruding cohesins. These loops and domains are thought to play critical roles in regulating gene expression by regulating long-range enhancer-promoter interactions. But whether CTCF/cohesin loops are stable or dynamic structures was unknown. First, we will discuss our recent work (Gabriele et al. Science 2022) directly visualizing these chromatin loops using super-resolution live-cell imaging. This lead to the surprising finding that CTCF/cohesin loops are both very rare and dynamic calling into question the model that these loops stably regulate enhancer-promoter interactions. Second, we will discuss our recent development of Region Capture Micro-C (RCMC) to study enhancer-promoter interactions at extremely high-resolution (Goel et al. BioRxiv 2022). Using RCMC, we surprisingly found that most enhancer-promoter interactions are insensitive to loss of cohesin and to transcriptional inhibition. This has lead us to propose a model whereby enhancer-promoter interactions are formed through a compartmentalization mechanism - specifically block co-polymer microphase separation - and wherein loop extrusion plays only a minor role in regulating most enhancer-promoter interactions. Finally, we will present our updated understanding on the relationship between 3D genome structure and function.