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

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, ChIP-Seq, and ATAC-Seq showed TAZ-CAMTA1 and YAP-TFE3 transcriptional programs overlap with TAZ and YAP but also drive expression of a novel transcriptome. The altered transcriptional program of the fusion proteins owing to altered DNA binding as well as shifts in the chromatin landscape. Overall design: Transcriptionally accessible chromatin of SW872 liposarcoma cells transduced with fusion gene constructs generated by treatment with transposase and subsequent deep sequencing, in triplicate, using Illumina HiSeq4000.