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Activity-by-contact model of enhancer-promoter regulation from thousands of CRISPR perturbations

Nat Genet.. 2019; 
Fulco CP1,2, Nasser J1, Jones TR1, Munson G1, Bergman DT1, Subramanian V1, Grossman SR1,3, Anyoha R1, Doughty BR1, Patwardhan TA1, Nguyen TH1, Kane M1, Perez EM1, Durand NC1,4,5,6, Lareau CA1, Stamenova EK1, Aiden EL1,4,5,6,7, Lander ES8,9,10, Engreitz JM11,12.
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摘要

Enhancer elements in the human genome control how genes are expressed in specific cell types and harbor thousands of genetic variants that influence risk for common diseases1-4. Yet, we still do not know how enhancers regulate specific genes, and we lack general rules to predict enhancer-gene connections across cell types5,6. We developed an experimental approach, CRISPRi-FlowFISH, to perturb enhancers in the genome, and we applied it to test >3,500 potential enhancer-gene connections for 30 genes. We found that a simple activity-by-contact model substantially outperformed previous methods at predicting the complex connections in our CRISPR dataset. This activity-by-contact model allows us to construct ge... More

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