SEdb 3.0: a comprehensive super-enhancer database across multiple species

Super-enhancers (SEs) are key DNA cis-regulatory elements that play a central role in regulating tissue/cell-specific gene expression, thereby maintaining cellular identity and function. SEdb 3.0 (http://www.licpathway.net/sedb) provides an extensively updated resource of SEs and their regulatory annotations across multiple species. The current version of SEdb now curates 3 478 186 SEs from 5387 H3K27ac ChIP-seq samples across four species. Compared to SEdb 2.0, it has achieved a two-fold expansion in human and mouse SE entries while newly incorporating Arabidopsis thaliana and maize data, significantly enhancing both the database's scale and its utility in plant research. Furthermore, abundant (epi)genomic features have been added, such as enhancer RNAs (eRNAs), binding sites of transcription co-factors (TcoFs), and chromatin regulators (CRs). The inclusion of eRNAs provides insights into SE transcriptional activity. Mapping TcoF binding sites highlights their roles in mediating enhancer-promoter looping and stabilizing transcriptional complexes at SEs. The integration of CRs uncovers how SEs are associated with histone modifications and chromatin remodeling, which are critical for maintaining an open chromatin state. Collectively, these annotations not only reveal the diverse mechanisms by which SEs exert regulatory functions but also enable more detailed investigations into their biological significance and functional roles. Meanwhile, existing annotations have been substantially expanded, such as an approximately five-fold increase in transcription factor (TF) ChIP-seq data, a 2.3-fold rise in TF motifs, and a roughly 1.8-fold growth in SE-associated eQTL-gene regulatory pairs. SEdb 3.0 introduces two advanced inference strategies for associating genes with SEs. Moreover, two newly developed analysis tools are provided in SEdb 3.0, including SE blast alignment analysis and SE-driven core TF enrichment analysis. In summary, SEdb 3.0 represents a significant upgrade over SEdb 2.0, with a substantial expansion in SE coverage across multiple species, alongside enhanced functional annotations encompassing SE upstream/downstream regulatory information, thereby offering a more comprehensive and user-friendly platform for exploring the biological roles of SEs.