The study investigates the transcriptional regulation of YAP/TAZ, key effectors of the Hippo pathway, by analyzing their binding sites in breast cancer cells using ChIP-seq. The authors find that YAP/TAZ primarily bind to enhancers through TEAD factors, forming a complex with AP-1 (a dimer of JUN and FOS proteins) at composite cis-regulatory elements. This complex synergistically activates genes involved in S-phase entry and mitosis, primarily from distal enhancers that contact target promoters via chromatin looping. The oncogenic growth driven by YAP/TAZ is significantly enhanced by AP-1 and reduced by its loss. Conversely, AP-1-promoted skin tumorigenesis is prevented in YAP/TAZ conditional knockout mice. These findings highlight a novel layer of signaling integration involving YAP/TAZ and AP-1, providing new insights into the transcriptional regulation of cell proliferation and tumor growth.The study investigates the transcriptional regulation of YAP/TAZ, key effectors of the Hippo pathway, by analyzing their binding sites in breast cancer cells using ChIP-seq. The authors find that YAP/TAZ primarily bind to enhancers through TEAD factors, forming a complex with AP-1 (a dimer of JUN and FOS proteins) at composite cis-regulatory elements. This complex synergistically activates genes involved in S-phase entry and mitosis, primarily from distal enhancers that contact target promoters via chromatin looping. The oncogenic growth driven by YAP/TAZ is significantly enhanced by AP-1 and reduced by its loss. Conversely, AP-1-promoted skin tumorigenesis is prevented in YAP/TAZ conditional knockout mice. These findings highlight a novel layer of signaling integration involving YAP/TAZ and AP-1, providing new insights into the transcriptional regulation of cell proliferation and tumor growth.