enhancer3D: 3D chromatin structures and enhancer-promoter distance profiles for archaic and modern human genomes

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Spatial interactions between enhancers and promoters (E-P) are fundamental to gene regulation, yet understanding their evolution, particularly in the context of human divergence and uniqueness, remains a significant challenge. To address this, we present enhancer3D, which is, to our knowledge, the first publicly accessible database of 3D chromatin model ensembles for archaic (Neanderthal and Denisovan) and modern human genomes. The resource enables comparative analysis of E-P spatial distance profiles across evolutionary lineages and between different modern human cell lines (GM12878, HFFc6, and H1-ESC). This facilitates novel investigations into how structural variants and evolutionary divergence impact gene regulation by altering 3D chromatin conformation. For improved user usability, enhancer3D offers an intuitive web interface with integrated visualisation tools, including an embedded IGV genome browser for genomic context and an NGL viewer for interactive exploration of 3D models. All models and datasets are freely available at https://3dgnome.mini.pw.edu.pl/enhancer3D/.

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