Extended Data Fig. 4: CRISPRi screen of EIEs in COLO320DM for different timepoints.

a. Schematic of the CRISPRi screening strategy used to evaluate the regulatory potential of the 68 EIEs by designing 4-6 gRNAs per element for a total of 257 genomic regions tested and 125 non-targeting control sgRNAs. The screen involved the transduction of cells with a lentivirus expressing dCas9-KRAB and the sgRNAs such that each cell received 1 sgRNA, followed by calculation of cell growth phenotype over a series of time points (Baseline(4 days), Baseline + 3 days, Baseline + 14 days, and Baseline + 1 month). The screen was further filtered on guide specificity (methods) and 36/68 targeted EIEs met the qualifying threshold. b. The growth phenotype of COLO320DM cells and reproducibility of counts between two biological replicates at different timepoints for the 36 qualifying EIEs. Each point represents the average guide effect (Z-score). Pearson correlations (r) are reported for reproducibility plots. c. Growth phenotypes of the qualifying EIE-targeting guides in COLO320DM cells across multiple time points. Each point represents the average guide effect (Z-score) for sgRNAs targeting a specific EIE. Guides with an average abs(Z-score) > 1 are annotated.