Liquid condensates: a new barrier to loop extrusion?

Liquid-liquid phase separation (LLPS), driven by dynamic, low-affinity multivalent interactions of proteins and RNA, results in the formation of macromolecular condensates on chromatin. These structures are likely to provide high local concentrations of effector factors responsible for various processes including transcriptional regulation and DNA repair. In particular, enhancers, super-enhancers, and promoters serve as platforms for condensate assembly. In the current paradigm, enhancer-promoter (EP) interaction could be interpreted as a result of enhancer- and promoter-based condensate contact/fusion. There is increasing evidence that the spatial juxtaposition of enhancers and promoters could be provided by loop extrusion (LE) by SMC complexes. Here, we propose that condensates may act as barriers to LE, thereby contributing to various nuclear processes including spatial contacts between regulatory genomic elements.