Sister chromatid cohesion–independent functions of the cohesin complex. (A) Cohesin mutations lead to increased intermixing of transcriptionally active A compartments and transcriptionally inactive B compartments. (B) Cohesin-mutant cells preserve TAD boundaries, albeit with weaker insulation, extrude longer loops and lose a subset of shorter E-P loops, which drives transcriptional changes. STAG1-cohesin is recruited to maintain chromatin organization in STAG2-mutant cells. (C) Cohesin is recruited along with the PRC complex to mediate epigenetic silencing of the HOX gene cluster at the level of nucleosomes.