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An integrative approach utilizing RNA-Seq, ChIP-Seq, and ATAC-Seq to dissect the oncogenic mechanisms of the TAZ-CAMTA1 and YAP-TFE3 fusion proteins

 Munir Tanas, Assistant Professor, Department of Pathology

TAZ (WWTR1) and YAP are oncogenic transcriptional coactivators negatively regulated by the Hippo signaling pathway. They are constitutively activated in many cancers including sarcomas, however genetic alterations of TAZ and YAP are rare. Epithelioid hemangioendothelioma is a vascular sarcoma, 90% of which contain a WWTR1-CAMTA1 gene fusion while 10% contain a YAP1-TFE3 gene fusion.  The precise mechanism by which TAZ-CAMTA1 (TC) and YAP-TFE3 (YT) transform cells is poorly understood. A combined BioID mass spectrometry/RNAi screen demonstrated that the TC and YT interact with multiple epigenetic modifiers including subunits of the Ada2a-containing (ATAC) histone acetyltransferase complex.  An integrative approach utilizing RNA-Seq, ChIP-Seq, and ATAC-Seq has yielded insights into how the interaction of the fusion proteins with these epigenetic modifiers alters the basal TAZ/YAP transcriptional program.