Modeling how gene switches control gene activity using thousands of CRISPR experiments

More than 3,500 potential enhancer-gene connections were tested using a novel approach called CRISPRi-FlowFISH.

• Enhancer elements in the genome influence gene expression and are associated with genetic variants linked to common diseases.
• Current understanding of how enhancers regulate specific genes is limited, with a lack of general predictive rules.
• The activity-by-contact model significantly improved predictions of enhancer-gene connections compared to previous methods.
• This model enables the creation of genome-wide maps of enhancer-gene connections based on chromatin state measurements.
• The findings could aid in interpreting the functions of numerous disease risk variants located in noncoding regions of the genome.

Simplified