Our findings raise several questions including whether the changes observed in active histone marks, chromatin accessibility, and de-repression of ERVs after Atrx KO occur through direct or indirect mechanisms and how these epigenetic changes contribute to the pathogenesis or may invoke therapeutic opportunities in sarcomas in which ATRX loss is common (e.g., UPS and leiomyosarcoma). This evidence concerns the gene ATRX and sarcoma.