The TAZ-CAMTA1 and YAP-TFE3 fusion proteins modulate the basal TAZ/YAP transcriptional program by recruiting the Ada2a-containing histone acetyltransferase complex [ChIP-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 validating the chromatin occupancy of TAZ-CAMTA1 and YAP-TFE3 with distal regulatory elements, such as enhancer regions marked by the presence of H3K27ac marks. The altered transcriptional program of the fusion proteins owing to altered DNA binding as well as shifts in the chromatin landscape. H3K27ac ChIP-seq profiles of SW872 liposarcoma cells transduced with fusion gene constructs and full length controls were generated by deep sequencing, in biological duplicate.