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Calling Cards is a platform technology to record a cumulative history of transient protein‐DNA interactions in the genome of genetically targeted cell types. The record of these interactions is recovered by next‐generation sequencing. Compared with other genomic assays, readouts of which provide a snapshot at the time of harvest, Calling Cards enables correlation of historical molecular states to eventual outcomes or phenotypes. To achieve this, Calling Cards uses the piggyBac transposase to insert self‐reporting transposon “Calling Cards” into the genome, leaving permanent marks at interaction sites. Calling Cards can be deployed in a variety of in vitro and in vivo biological systems to study gene regulatory networks involved in development, aging, and disease. Out of the box, it assesses enhancer usage but can be adapted to profile‐specific transcription factor (TF) binding with custom TF‐piggyBac fusion …