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 prot...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 TFenhancer-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.Database URL:http://lcbb.swjtu.edu.cn/EnhFFL/.展开更多
基金The research was supported by the Basic Research Cultivation Support Programof Fundamental Research Funds for the Central Universities,the National Natural Science Foundation of China(Grant No.32071343)the Sichuan Science and Technology Program(Grant No.2021YJ0048).
文摘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 TFenhancer-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.Database URL:http://lcbb.swjtu.edu.cn/EnhFFL/.
