The TAZ-CAMTA1 and YAP-TFE3 fusion proteins modulate the basal TAZ/YAP transcriptional program by recruiting the Ada2a-containing histone acetyltransferase complex [RNA-seq]

The WWTR1(TAZ)-CAMTA1 and YAP1-TFE3 gene fusions are disease defining gene alterations for epithelioid hemangioendothelioma, a vascular cancer. The resultant fusion proteins fuse the C terminus of CAMTA1 and TFE3 in frame to the N terminus of TAZ and YAP, respectively. An unbiased BioID-mass spectrometry/RNAi screen identified YEATS2 and ZZZ3 as components of the Ada2a-containing histone acetyltransferase complex and key interactors of both TAZ-CAMTA1 and YAP-TFE3. An integrative NGS approach including RNA-Seq and ATAC-Seq showed that the differentially expressed genes in YAP-TFE3 cells with knockdown of YEATS2 or ZZZ3 are nested in regions of open chromatin unique to YAP-TFE3. The altered transcriptional program of the fusion proteins is modulated by the Ada2a-containing histone acetyltransferase complex. Overall design: mRNA profiles of SW872 liposarcoma cells transduced with fusion gene constructs with shRNAs targeting YEATS2 or ZZZ3 were generated by deep sequencing, in duplicate.