This study reveals a novel mechanism by which YAP/TAZ and AP-1 transcription factors collaborate to drive oncogenic growth. YAP/TAZ are nuclear effectors of the Hippo pathway that regulate organ growth and tumorigenesis. Through chromatin immunoprecipitation and sequencing (ChIP-seq), the researchers identified that YAP/TAZ bind to DNA through TEAD factors, which co-occupy chromatin with AP-1 at composite cis-regulatory elements. This complex synergistically activates genes involved in cell cycle progression and mitosis, primarily from distal enhancers that interact with target promoters via chromatin looping. YAP/TAZ-induced oncogenic growth is enhanced by AP-1 gain and suppressed by its loss, while AP-1-promoted skin tumorigenesis is prevented in YAP/TAZ conditional knockout mice. The study highlights a new layer of signaling integration, where YAP/TAZ function at the chromatin level is regulated by AP-1. YAP/TAZ are potent inducers of cell proliferation and are important drivers of tumorigenesis in various contexts. However, the mechanisms underlying their activity remain unclear. The study identifies that YAP/TAZ bind to DNA through TEAD factors, and that AP-1 factors co-occupy these regions, forming a transcription factor complex that regulates gene expression. The study also shows that YAP/TAZ and AP-1 cooperate to promote oncogenic growth, with AP-1 being essential for YAP/TAZ-dependent gene expression and tumorigenesis. The findings suggest that YAP/TAZ and AP-1 work together to drive cell proliferation and tumorigenesis, with AP-1 playing a critical role in the transcriptional and biological effects of YAP/TAZ. The study also demonstrates that YAP/TAZ are required for AP-1-driven tumorigenesis, as YAP/TAZ-deficient mice show reduced tumorigenesis in the DMBA/TPA model of skin tumorigenesis. The results highlight the importance of YAP/TAZ and AP-1 in oncogenic growth and suggest that targeting these pathways could be a potential therapeutic strategy.This study reveals a novel mechanism by which YAP/TAZ and AP-1 transcription factors collaborate to drive oncogenic growth. YAP/TAZ are nuclear effectors of the Hippo pathway that regulate organ growth and tumorigenesis. Through chromatin immunoprecipitation and sequencing (ChIP-seq), the researchers identified that YAP/TAZ bind to DNA through TEAD factors, which co-occupy chromatin with AP-1 at composite cis-regulatory elements. This complex synergistically activates genes involved in cell cycle progression and mitosis, primarily from distal enhancers that interact with target promoters via chromatin looping. YAP/TAZ-induced oncogenic growth is enhanced by AP-1 gain and suppressed by its loss, while AP-1-promoted skin tumorigenesis is prevented in YAP/TAZ conditional knockout mice. The study highlights a new layer of signaling integration, where YAP/TAZ function at the chromatin level is regulated by AP-1. YAP/TAZ are potent inducers of cell proliferation and are important drivers of tumorigenesis in various contexts. However, the mechanisms underlying their activity remain unclear. The study identifies that YAP/TAZ bind to DNA through TEAD factors, and that AP-1 factors co-occupy these regions, forming a transcription factor complex that regulates gene expression. The study also shows that YAP/TAZ and AP-1 cooperate to promote oncogenic growth, with AP-1 being essential for YAP/TAZ-dependent gene expression and tumorigenesis. The findings suggest that YAP/TAZ and AP-1 work together to drive cell proliferation and tumorigenesis, with AP-1 playing a critical role in the transcriptional and biological effects of YAP/TAZ. The study also demonstrates that YAP/TAZ are required for AP-1-driven tumorigenesis, as YAP/TAZ-deficient mice show reduced tumorigenesis in the DMBA/TPA model of skin tumorigenesis. The results highlight the importance of YAP/TAZ and AP-1 in oncogenic growth and suggest that targeting these pathways could be a potential therapeutic strategy.