Our latest publication in @NatureComms “Loss of cohesin regulator PDS5A reveals repressive role of Polycomb loops” advances our understanding of epigenetic gene regulation.

Using a CRISPR screen, we found that PDS5A is a key player linking Polycomb-mediated silencing and 3D genome organization. Deletion of PDS5A disrupts cohesin activity, leading to unique genome architecture and the loss of ultra-long Polycomb loops, impacting gene silencing.
Here are the key findings of our paper:

• Using a CRISPR screen in mouse embryonic stem cells, we discovered that the cohesin regulator PDS5A plays a pivotal role in connecting Polycomb-mediated gene silencing with 3D genome organization. This is a crucial link in the intricate dance of gene regulation.
• Deleting PDS5A has profound effects! It impairs cohesin unloading, leading to the derepression of a specific subset of endogenous PRC1/PRC2 target genes. Importantly, this derepression is not tied to the loss of Polycomb chromatin domains, unraveling a novel layer of gene control.
• PDS5A removal doesn’t just stop at gene derepression. It triggers aberrant cohesin activity, resulting in the formation of ectopic insulation sites. These sites disrupt the formation of ultra-long Polycomb loops, essential for robust silencing at a subset of PRC1/PRC2 target genes.
• Why do Polycomb loops matter? Our study reveals their crucial role in maintaining robust silencing at specific target genes. The disruption caused by PDS5A removal highlights the intricate balance required for effective Polycomb regulation.
• In conclusion, our research demonstrates that maintaining cohesin-dependent genome architecture is critical for Polycomb regulation. This finding opens new avenues for understanding the complexities of gene regulation and has broad implications across the field of genomics.