Cohesin mediated loop extrusion from active enhancers form chromatin jets inC. elegans

Abstract

AbstractIn mammals, cohesin and CTCF organize the 3D genome into topologically associated domains (TADs) to regulate communication between cis-regulatory elements. However, many organisms, includingS. cerevisiae, C. elegans, andA. thalianalack CTCF. Here, we useC. elegansas a model to investigate the function of cohesin in 3D genome organization in an animal without CTCF. We use auxin-inducible degradation to acutely deplete SMC-3 or its negative regulator WAPL-1 from somatic cells. Using Hi-C data, we identify a cohesin-dependent 3D genome feature termed chromatin jets (aka fountains), also observed in zebrafish and mammalian genomes. The jets emerge from NIPBL occupied segments, and the trajectory of the jets coincides with cohesin binding. The spreading of cohesin from jet origins depends on a fully intact cohesin complex and is extended upon WAPL-1 depletion. These results support the idea that cohesin is preferentially loaded at NIPBL occupied sites, from which cohesin loop extrudes in an effectively two-sided manner. The location of putative loading sites coincides with active enhancers and the pattern of chromatin jets correlates with transcription. We propose that in the absence of CTCF, preferential loading of cohesin at enhancers is a conserved mechanism of genome organization that regulates the interaction of gene regulatory elements in 3D.