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

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.