EnhancerDB 2.0: a comprehensive cross-species enhancer atlas

Enhancers are evolutionarily conserved cis-regulatory elements that drive spatiotemporal gene expression programs underlying development, adaptation, and phenotypic diversity. To clarify the function and regulatory network of enhancers and driven by the rapid growth of large-scale omics data, we developed EnhancerDB 2.0 as an updated version of EnhancerDB 1.0 to facilitate comprehensive profiling of enhancer regulatory networks and multi-omics interpretation of gene regulation. EnhancerDB 2.0 has been expanded from a single human species to five species (human, mouse, zebrafish, fruit fly, and yeast), with the total number of enhancer entries reaching 1,605,856. The database also now provides substantially enriched annotations, including transcription factor binding sites, target genes/miRNAs/lncRNAs, SNPs, CRISPR-Cas9 target sites, chromatin accessibility regions, repeat regions, methylation sites, and GWAS entries, with nearly 100 million annotated entries in total. Furthermore, EnhancerDB 2.0 also features an improved search function and a new analysis module capable of generating publication-quality charts. In summary, EnhancerDB 2.0 provides a user-friendly platform for exploring enhancer-mediated regulation and serves as a valuable resource for researchers in biology, medicine, genetics, and related fields.