promoter activity, along with measures of transcription factor activity and evolutionary conservation.Table 1 Computational approaches to predicting gene targets of enhancer elements Reference or method Input data required Gene expression Linear model Number of genes with predictions (per cell line) FDR Species Publically available Nearest geneNoneNot consideredNearest geneNA~40% to 73%AnyNANearest expressed geneGene expressionConsideredNearest expressed geneNA~53% to 77%AnyNAErnst et al. [21]H3K4me1, H3K4me2, H3K27ac, RNA-seqConsideredDistance based (125 kb)NANot determinedHumanNoThurman et al. [66]DNase I hypersensitivityNot consideredDistance based (500 kb)NANot determinedHumanNoSheffield et al. [70]DNase I hypersensitivity and RNA-seqConsidered100 kbNANot determinedHumanPredicted interactions: [http://dnase.genome.duke.edu/]Shen et al. [67]H3K4me1, H3K27ac, RNA Pol IINot consideredTopological domain based5,000 to 8,000Not determinedMouseNoAndersson et al. [16]CAGEConsidered500 kbNANot determinedHumanNoPreSTIGE [7]H3K4me1ConsideredDistance (100 kb) and CTCF based3,000 to 5,000~13% to 23%HumanPredicted interactions: http://genetics.case.edu/prestige Method application: http://prestige.case.edu PreSTIGEouse [68]H3K4me1ConsideredDistance based (100 kb)3,000 to 5,000Not determinedMousePredicted interactions: http://genetics.case.edu/prestige Method application: http://prestige.case.edu IM-PET [69]H3K4me1, H3K27ac, H3K4me3 and RNA-seq*ConsideredDistance (2 Mb)7,000 to 10,000~1%HumanMethod application: http://www.healthcare.uiowa.edu/labs/tan/IM-PET.html *Input data utilized in publication, other input options exist. CAGE, cap analysis of gene expression; CTCF, CCCTC-binding factor (zinc finger protein demonstrated to function as an insulator protein); FDR, false discovery rate; Mb, megabases; NA, not applicable; RNA-seq, RNA sequencing.
