The TAZ-CAMTA1 and YAP-TFE3 fusion proteins modulate the basal TAZ/YAP transcriptional program by recruiting the Ada2a-containing histone acetyltransferase complex [rnaseq_sw872]. The TAZ-CAMTA1 and YAP-TFE3 fusion proteins modulate the basal TAZ/YAP transcriptional program by recruiting the Ada2a-containing histone acetyltransferase complex [rnaseq_sw872]

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: mRNA profiles of SW872 liposarcoma 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——一类血管源性恶性肿瘤——的疾病决定性基因改变。由此产生的融合蛋白分别将CAMTA1与TFE3的C端按读码框与TAZ和YAP的N端进行融合。通过无偏倚的BioID-质谱/RNA干扰（RNAi）筛选，研究者鉴定出YEATS2与ZZZ3是含Ada2a的组蛋白乙酰转移酶复合物的组成成分，同时也是TAZ-CAMTA1与YAP1-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，研究发现TAZ-CAMTA1与YAP1-TFE3的转录调控程序既与TAZ和YAP的转录程序存在重叠，同时也可驱动一套全新的转录组表达谱。融合蛋白的转录程序发生改变，这源于其DNA结合特性的改变以及染色质调控图谱的动态变化。整体实验设计：采用Illumina HiSeq4000测序平台，对转导融合基因构建体的SW872脂肪肉瘤细胞进行深度测序，设置三次生物学重复，以获取其mRNA表达谱。