ORCA-mediated Polycomb Repressive Complex stabilization maintains 3D-genome architecture and controls replication timing [Cut & Run]

Predominantly, in transformed cells, PcG bodies form distinct nuclear foci, within which PcG-bound DNA is localized. These structures likely represent misregulated gene expression due to the loss of normal regulatory mechanisms, yet the molecular function of these bodies in cellular homeostasis remains unknown.

Using TSA-Seq (Tyramide signal amplification), we provide the first-of-a-kind comprehensive view of the genomic regions, including specific centromeric and telomeric sites that are in proximity to the PcG bodies. Further, these regions are enriched for the repressive histone marks, H3K27me3, H3K9me3 and depleted for active marks, H3K4me3 consistent with a lack of accessible chromatin. We find high density of replication origins around PcG bodies, consistent with the replication factor, ORCA/LRWD1 localizing at these sites.