HIF2ɑ Requires Engagement with YAP/TAZ and AP-1 Transcription Factors to Maintain Oncogenic Transcription in Clear Cell Renal Cell Carcinoma [CUT&Tag]

Integrated analysis of public ccRCC multi-omic datasets revealed frequent inactivation of the Hippo tumor suppressor pathway and corresponding increase in YAP/TAZ transcription activity in ccRCC tumors, which is associated with worse overall survival in treatment naïve patients.

By combining Cut&Tag and BRB-seq analysis, we assessed the chromatin binding and gene regulation of YAP and HIF2ɑ, and unveiled that these two proteins are co-recruited to AP-1 sites through interactions with the AP-1 transcription factors. YAP/TAZ, HIF2ɑ and JUN are dependent on each other to maintain their expression, and function cooperatively to promote the expression of highly expressed transcription factors and other important oncogenes.