What Is the Role of Cohesin in Transcription Regulation?

Available experimental data do not yet permit an unambiguous or comprehensive answer to the question posed in the title. A conventional approach to determining the role of a particular protein in cellular processes is to remove or inactivate it. However, transcriptome analyses following cohesin depletion have yielded markedly different results depending on the used experimental strategy, including conditional genetic knockout, RNA interference, and rapid inducible degradation systems. From a historical perspective, we examined why, until the mid-2010s, cohesin had been widely regarded as a major regulator of transcription and why later, this conclusion could no longer be maintained with the same degree of certainty. Recent observations suggest that a coherent understanding of cohesin's role in transcriptional regulation may emerge from two complementary developments: the recent discovery of new classes of genomic elements and detailed analyses of the genetic architecture of individual loci exhibiting distinct responses to cohesin depletion or to inhibition of cohesin-mediated extrusion.