Alterations in Spatial Genome Compartmentalization Associated with Constriction and Expansion

The May 2023 Monthly Seminar on Physical Genomics features Dr. Rachel Patton McCord, Assistant Professor of Biochemistry & Cellular and Molecular Biology at the University of Tennessee.
Abstract
It has become increasingly clear that the 3D folding of human chromosomes inside the cell nucleus affects numerous fundamental biological processes, including gene regulation, DNA repair and replication, and even the physical properties of the nucleus. Recent research is beginning to define the key molecular factors that build genome structure, but less is known about how this structure responds to physical stresses experienced by cells and nuclei. The 3D genome structure in healthy cells must withstand or respond to perturbations such as physical forces and nuclear shape changes. Disruptions in genome structure and nuclear architecture can lead to diseases such as cancer or premature aging, and so Dr .McCord's research seeks to determine the characteristics, causes, and effects of these 3D genome changes. By integrating microscopy, computational analysis, and the sequencing-based technique chromosome conformation capture (Hi-C) approach, her lab probes the properties of human 3D genome architecture in conditions such as cell migration through narrow constrictions and direct expansion of isolated nuclei in low salt. Her work shows striking differences in chromosome spatial compartmentalization in melanoma cells that have passed repeatedly through tight constrictions. These constricted migration 3D genome signatures likely arise through a combination of both selection and changes induced by the constricted migration process. Some chromosome structure shifts are associated with altered gene expression while others may be more physical in nature. A loss of interaction frequency within heterochromatic regions is a shared feature between melanoma and breast cancer cells. When nuclei are instead expanded by decompacting the chromatin fiber in low salt, an overall preservation of chromosome contacts across length scales is observed, but also a similar loss of heterochromatic compartment strength as was observed after constricted migration. These observations begin to shed light on the robustness of the 3D genome structure to perturbation and how the network of 3D contacts in the genome can accomplish both gene regulatory functions and contribute to necessary physical properties of the nucleus.
Sponsored by the Center for Physical Genomics and Engineering at Northwestern University and the Robert H. Lurie Comprehensive Cancer Center.

[@EdT.-xt6yv]

14:20 spatial compartment 17:00 compartmental,cell types 20:30 migration,expression GENE 25:00 contact loss in b compartment 29:00 💹expansion INHIBITOR 32:39 TOPOLOGY [✓]