TY - JOUR T1 - Cohesin disrupts polycomb-dependent chromosome interactions JF - bioRxiv DO - 10.1101/593970 SP - 593970 AU - JDP Rhodes AU - A Feldmann AU - B Hernández-Rodríguez AU - N Díaz AU - JM Brown AU - NA Fursova AU - NP Blackledge AU - P Prathapan AU - P Dobrinic AU - M Huseyin AU - A Szczurek AU - K Kruse AU - KA Nasmyth AU - VJ Buckle AU - JM Vaquerizas AU - RJ Klose Y1 - 2019/01/01 UR - http://biorxiv.org/content/early/2019/03/30/593970.abstract N2 - How chromosome organisation is related to genome function remains poorly understood. Cohesin, loop-extrusion, and CTCF have been proposed to create structures called topologically associating domains (TADs) to regulate gene expression. Here, we examine chromosome conformation in embryonic stem cells lacking cohesin and find as in other cell types that cohesin is required to create TADs and regulate A/B compartmentalisation. 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, depend on PRC1, and we discover that cohesin counteracts these interactions. This disruptive activity is independent of CTCF and TADs, and regulates gene repression by the polycomb system. Therefore, in contrast to the proposal that cohesin creates structure in chromosomes, we discover a new role for cohesin in disrupting polycomb-dependent chromosome interactions to regulate gene expression. ER -