Cohesin and Polycomb Proteins Functionally Interact to Control Transcription at Silenced and Active Genes

Abstract

Cohesin is crucial for proper chromosome segregation but also regulates gene transcription and organism development by poorly understood mechanisms. Using genome-wide assays in Drosophila developing wings and cultured cells, we find that cohesin functionally interacts with Polycomb group (PcG) silencing proteins at both silenced and active genes. Cohesin unexpectedly facilitates binding of Polycomb Repressive Complex 1 (PRC1) to many active genes, but their binding is mutually antagonistic at silenced genes. PRC1 depletion decreases phosphorylated RNA polymerase II and mRNA at many active genes but increases them at silenced genes. Depletion of cohesin reduces long-range interactions between Polycomb Response Elements in the invected-engrailed gene complex where it represses transcription. These studies reveal a previously unrecognized role for PRC1 in facilitating productive gene transcription and provide new insights into how cohesin and PRC1 control development.

Author Summary

An important task for the cohesin protein complex that binds chromosomes is to ensure equal distribution of chromosomes into the daughter cells when a cell divides. Small changes in cohesin activity, however, can alter gene activity without affecting chromosome distribution, and disrupt physical and mental development. How cohesin controls gene activity and development is not well understood. In this study we show that cohesin controls the binding of the Polycomb Repressive Complex 1 (PRC1) to many genes. PRC1 silences many genes that control development. Surprisingly, we find that cohesin aids binding of PRC1 to active genes, where PRC1 ensures that RNA polymerase, the enzyme that transcribes genes, is properly modified before entering the gene body. We also find that cohesin antagonizes the binding and activity of PRC1 at genes silenced by PRC1, and can influence interactions between the DNA sequences that recruit PRC1 and other Polycomb complexes to silenced genes. These findings provide new and unexpected insights into how both cohesin and PRC1 control gene activity during development.