148 Oral - Chromatin
Saturday April 09, 9:00 AM - 9:15 AM
Condensin II loss ameliorates long-range chromosomal interactions in both active and inactive physical compartments within a chromosome territory
Authors: Randi Isenhart 1; Son Nguyen 1; Leah Rosin 1; Olivia Crocker 1; Yemin Lan 2; Eric Joyce 1
Affiliations: 1) Department of Genetics, Perelman School of Medicine, University of Pennsylvania; 2) Department of Cell and Developmental Biology, Perelman School of Medicine, University of Pennsylvania
Keywords: k. nuclear organization; f. insulators/boundary elements
Metazoan genomes are folded into structures at a variety of length-scales, from chromatin loops and domains to higher-order interactions that connect distal genomic regions to form chromosome territories. Polymer modeling of Hi-C data suggests that chromosome folding is driven by a loop extrusion mechanism to both fold entire chromosomes into territories and restrict their interactions with other chromosomes. Recent work from our lab and others suggest that the condensin II loop-extruding complex specifically regulates chromosome territory formation and levels of inter-chromosomal interactions during interphase in Drosophila and human cells. To dissect the mechanism by which condensin II modulates genome folding, we are using a combination of Oligopaint FISH and Hi-C in Drosophila cultured cells to show that condensin II is required for proper inter-domain interactions in a chromatin state-nonspecific manner without altering interactions within domains. Optimized ChIP-Seq of a condensin II component reveals a novel class of genomic binding sites that are associated with long chromatin loops and colocalize with the gypsy complex, a strong insulator at the interface of active and inactive chromatin. In vivo data suggest that these condensin II-dependent interactions are important for proper silencing of heterochromatic sequences that are distal, but not proximal, to the pericentromeric heterochromatin. Overall, we propose a model in which condensin II extrudes chromatin into large loops until blocked by an insulator prior to cohesin activity early in interphase, thereby bridging distal interactions that fold chromosomes into distinct territories. Ongoing experiments will determine the functional consequences of condensin II loss on gene regulation.