Summary: How chromosome organization is related to genome function remains poorly understood.Cohesin, loop extrusion, and CCCTC-binding factor (CTCF) have been proposed to create topologically associating domains (TADs) to regulate gene expression.Here, we examine chromosome conformation in embryonic stem cells lacking cohesin Clothing - Mens Tops - Hoodies and find, as in other cell types, that cohesin is required to create TADs and regulate A/B compartmentalization.However, in the absence of cohesin, we identify a series of long-range chromosomal interactions that persist.
These correspond to regions of the genome occupied by the polycomb repressive system and are dependent on PRC1.Importantly, we discover that cohesin counteracts these polycomb-dependent interactions, but not interactions between super-enhancers.This disruptive activity is independent of CTCF and insulation and appears to modulate gene repression by the polycomb system.Therefore, we discover that cohesin disrupts polycomb-dependent chromosome interactions to modulate gene expression in embryonic stem cells.
: Using Hi-C, Capture-C, and DNA-FISH, Rhodes et al.discover that interactions between polycomb target DETANGLING SPRAY genes occur independently of cohesin in embryonic stem cells.This relies on PRC1, and these interactions are disrupted by cohesin-mediated loop extrusion.Upon removal of cohesin, gene repression is enhanced at polycomb-occupied genes with increased interactions.
Keywords: cohesin, Polycomb, TADs, loop extrusion, Hi-C, gene regulation.