Fig. 2. Seven approaches for characterizing non-coding genetic variants.

Genomic assays (left), the coverage of all common genetic variants in the 605 kb locus (middle), and whether the assay is specific to genomic regions or variants (right), grouped into observational (top) and perturbational assays (bottom). (1) HiChIP can be used to identify active chromatin regions (H3K27ac labeled) that interact with the TNFAIP3 promoter. (2) DHS and ATAC-seq can be used to identify regions of accessible chromatin. (3) Variants predicted to alter TF binding can be identified using motif analysis in combination with evidence of TF binding by ChIP-seq⁴². Also see Supplementary Data 3–9. (4 and 5) Pooled CRISPRi and CRISPRa screens can determine regulatory potential of each region by repressing (CRISPRi) or artificially inducing (CRISPRa) each targeted region. (6 and 7) MPRA (with lentiviral or transfection delivery strategies) can be used to test for allele-specific reporter expression.