EnhFFL: A database of enhancer mediated feed-forward loops for human and mouse

Feed-forward loops (FFLs) are thought to be one of the most common and important classes of transcriptional network motifs involved in various diseases. Enhancers are cis-regulatory elements that positively regulate protein-coding genes or microRNAs (miRNAs) by recruiting DNA-binding transcription factors (TFs). However, a comprehensive resource to identify, store, and analyze the FFLs of typical enhancer and super-enhancer FFLs is not currently available. Here, we present EnhFFL, an online database to provide a data resource for users to browse and search typical enhancer and super-enhancer FFLs. The current database covers 46280/7000 TF-enhancer-miRNA FFLs, 9997/236 enhancer-miRNA-gene FFLs, 3561164/3193182 TF-enhancer-gene FFLs, and 1259/235 TF-enhancer feed-back loops (FBLs) across 91 tissues/cell lines of human and mouse, respectively. Users can browse loops by selecting species, types of tissue/cell line, and types of FFLs. EnhFFL supports searching elements including name/ID, genomic location, and the conservation of miRNA target genes. We also developed tools for users to screen customized FFLs using the threshold of q value as well as the confidence score of miRNA target genes. Disease and functional enrichment analysis showed that master miRNAs that are widely engaged in FFLs including TF-enhancer-miRNAs and enhancer-miRNA-genes are significantly involved in tumorigenesis.

Automated summary

EnhFFL is an online database providing data resource for users to browse and search typical enhancer and super-enhancer FFLs. The database covers a wide range of FFLs across different tissues/cell lines of human and mouse, allowing users to browse loops by selecting species, types of tissue/cell line, and types of FFLs. Disease and functional enrichment analysis revealed the significance of master miRNAs in FFLs in tumorigenesis.