ASPSCR1-TFE3 reprograms transcription by organizing enhancers around hexameric VCP [hASPS_ChIP, ASPL_VCP_Pol2]

Aberrant transcription in alveolar soft part sarcoma (ASPS) is orchestrated by the fusion oncoprotein, ASPSCR1-TFE3, product of a gene fusion created by a t(X;17) chromosomal translocation. Here, proteomics of proteins co-immunoprecipitating with ASPSCR1-TFE3 revealed strong enrichment of VCP/p97, an AAA+ ATPase with known segregase function. Positive and negative genetic experiments with ASPSCR1-TFE3 and VCP demonstrated that they function co-dependently for cancer cell proliferation, colony formation, enhancer activation, chromatin conformation, and transcription ASPS cell lines, tumor from ASPS mouse model and tumor from ASPS patients are used for ASPSCR1, VCP, POLII and various histone modification