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 Overall design: ASPS cell lines, tumor from ASPS mouse model and tumor from ASPS patients are used for ASPSCR1, VCP, POLII and various histone modification