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

bioRxiv [Preprint]. 2024 Mar 18:2023.09.18.558239. doi: 10.1101/2023.09.18.558239.

Abstract

In mammals, cohesin and CTCF organize the 3D genome into topologically associated domains (TADs) to regulate communication between cis-regulatory elements. However, many organisms, including S. cerevisiae, C. elegans, and A. thaliana lack CTCF. Here, we use C. elegans as 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 organization feature called chromatin jets (aka fountains). These are population average reflections of DNA loops that are ~20-40 kb in scale and often cover a few transcribed genes. The jets emerge from NIPBL occupied segments, and the trajectory of the jets coincides with cohesin binding. Cohesin translocation from jet origins depends on a fully intact complex and is extended upon WAPL-1 depletion. Hi-C results support the idea that cohesin is preferentially loaded at NIPBL occupied sites and loop extrudes in an effectively two-sided manner. The location of putative loading sites coincide with active enhancers and the strength of chromatin jet pattern correlates with transcription. Hi-C analyses upon WAPL-1 depletion reveal unequal loop extrusion processivity on each side and stalling due to cohesin molecules colliding. Compared to mammalian systems, average processivity of C. elegans cohesin is ~10-fold shorter and NIPBL binding does not depend on cohesin. We conclude that the processivity of cohesin scales with genome size; and regardless of CTCF presence, preferential loading of cohesin at enhancers is a conserved mechanism of genome organization that regulates the interaction of gene regulatory elements in 3D.

Publication types

  • Preprint