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You are here: Home / Teams / Physical Biology of Chromatin - D. Jost / Publications / Cohesin forms fountains at active enhancers in C. elegans.

Cohesin forms fountains at active enhancers in C. elegans.

Bolaji N Lüthi, Jennifer I Semple, Anja Haemmerli, Saurabh Thapliyal, Kalyan Ghadage, Klement Stojanovski, Dario D'Asaro, Moushumi Das, Nick Gilbert, Dominique A Glauser, Benjamin Towbin, Daniel Jost, and Peter Meister (2025)

Nat Commun, 17(1):681.

Transcriptional enhancers must locate target genes with precision. In mammals,topologically associating domains (TADs) guide this process, but the C. elegansgenome lacks such organization despite containing over 30,000 putative enhancers.Using high-resolution Hi-C, we identify distinct 3D chromatin structures aroundactive enhancers, termed fountains. These ~38 kb cohesin-dependent structures areunique to active enhancers and enriched for topoisomerases and negativelysupercoiled DNA, indicating topological stress. Disrupting cohesin collapsesfountains and leads to transcriptional upregulation of nearby genes, suggestingfountains act as spatial repressors controlling enhancer-promoter communication.This repression preferentially affects neuronal genes, including skn-1/Nrf, whichchanges isoform usage upon cohesin loss in ASI neurons. Cohesin cleavage alsoalters nematode movement and foraging behavior, linking 3D genome architecture toneural function and behavior. Thus, fountains represent a distinctive chromatinfeature that may ensure enhancer specificity in a TAD-less genome.

 
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