De novo formation of cis-regulatory contacts in the absence of NIPBL-driven chromatin loop extrusion.

Nature genetics
Authors
Abstract

NIPBL promotes chromatin loop extrusion by the cohesin complex until it stalls at convergently oriented CTCF sites, forming structural loops. While a large fraction of loops connecting cis-regulatory elements (CREs) can be maintained in cohesin-depleted cells, whether the loop extrusion process contributes to the de novo establishment of CRE loops remains unclear. To address this question, we characterized the formation of structural and CRE loops in NIPBL-depleted cells during the mitosis-to-G1-phase transition. Structural loop formation was impaired proportionally to loop length. Computational modeling supports these observations, suggesting that NIPBL promotes both cohesin loading and extrusion. Notably, most CRE loops, regardless of length, were established normally upon NIPBL degradation. While a subset of contacts among weak CREs were formed with delayed kinetics in NIPBL-depleted cells, generally gene activation was only mildly impaired. Collectively, our findings suggest that postmitotic establishment of regulatory contacts and gene transcription can occur independently of chromatin loop extrusion.

Year of Publication
2026
Journal
Nature genetics
Date Published
04/2026
ISSN
1546-1718
DOI
10.1038/s41588-026-02565-3
PubMed ID
41974991
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