The TAZ-CAMTA1 and YAP-TFE3 fusion proteins modulate the basal TAZ/YAP transcriptional program by recruiting the Ada2a-containing histone acetyltransferase complex [rnaseq_3T3]

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. mRNA profiles of NIH 3T3 cells transduced with fusion gene constructs were generated by deep sequencing, in triplicate, using Illumina HiSeq4000.

WWTR1(TAZ)-CAMTA1与YAP1-TFE3基因融合是上皮样血管内皮瘤（epithelioid hemangioendothelioma，一类血管源性癌症）的疾病定义性基因改变。所生成的融合蛋白分别将CAMTA1与TFE3的C端按读码框原位融合至TAZ和YAP的N端。通过无偏倚的BioID-质谱/RNA干扰（RNAi）筛选，鉴定出YEATS2与ZZZ3为含Ada2a的组蛋白乙酰转移酶复合物的组成组分，同时也是TAZ-CAMTA1和YAP-TFE3的关键互作蛋白。采用包含RNA测序（RNA-Seq）、染色质免疫沉淀测序（ChIP-Seq）以及转座酶可及性测序（ATAC-Seq）的整合下一代测序（NGS）策略分析显示，TAZ-CAMTA1与YAP-TFE3的转录程序既与TAZ和YAP的转录程序存在重叠，同时也可驱动产生一套全新的转录组。通过Illumina HiSeq4000平台开展三次生物学重复的深度测序，获取了转导融合基因构建体的NIH 3T3细胞的mRNA表达谱。