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bioRxiv · 10.64898/2026.01.06.697865

A cohesin-centric gene regulatory network resource with regulatory site annotations

Ding, J.·Chen, H.·Fu, Y.·Gao, W.·Fang, Z.·Wang, J.
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Abstract

Cohesin is a central regulator of transcription and chromatin organization, binding to the majority of cis-regulatory elements (CREs) and mediating enhancer-promoter communication through three-dimensional genome architecture. Although gene regulatory networks (GRNs) provide an interpretable framework for modeling transcriptional regulation, most existing GRN analyses focus on transcription factor (TF)-gene relationships and largely ignore regulatory sites. Consequently, cohesin-associated regulatory contexts are rarely incorporated into GRN reconstruction. Here, we present a cohesin-centric gene regulatory network database that explicitly integrates TF binding, regulatory sites, and gene targets into unified TF-site-gene regulatory paths. Building upon our previously developed multiomics resource CohesinDB, we mapped TF binding to cohesin-associated regulatory sites and linked these sites to their downstream target genes. The resulting Cohesin-GRN module in CohesinDB (http://cohesindb.wangjklab.com/) (http://120.24.147.32/)comprises 61,222,502 TF-cohesin site links and 2,228,634 cohesin site-gene links, collectively forming over 270 million TF-site-gene regulatory paths. By enabling a CRE-informed and site-aware representation of gene regulation, Cohesin-GRN bridges conventional TF-gene GRNs with regulatory site-centric mechanisms. Given the pervasive roles of cohesin in enhancer activity, transcriptional control, and human disease, Cohesin-GRN provides a valuable resource for exploring transcriptional dysregulation and gene regulatory networks.

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Ding, J., Chen, H., Fu, Y., Gao, W., Fang, Z., Wang, J.. 2026-01-07. A cohesin-centric gene regulatory network resource with regulatory site annotations. https://doi.org/10.64898/2026.01.06.697865

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