Super-enhancer-driven expression of BAHCC1 promotes melanoma cell proliferation and genome stability

• DOI: 10.1016/j.celrep.2023.113363
• Publication Date: 2023-11-03T04:36:49Z
• Authors: Pietro Berico; Maguelone Nogaret; Max Cigrang; Antonin Lallement; Fatemeh Vand-Raja...; Amanda Flores-Yanke; Giovanni Gambi; Guillaume Davidson; Leane Seno; Julian Obid; Bujamin H. Vokshi; Stephanie Le Gras; Gabrielle Mengus; Tao Ye; Carlos Fernandez ...; Mélanie Dalmasso; Emmanuel Compe; Corine Bertolotto; Eva Hernando; Irwin Davidson; Frédéric Coin
• Keywords: Microphthalmia-associated transcription factor; E2F

Super-enhancers (SEs) are stretches of enhancers ensuring a high level expression key genes associated with cell function. The identification cancer-specific SE-driven is powerful means for the development innovative therapeutic strategies. Here, we identify MITF/SOX10/TFIIH-dependent SE promoting BAHCC1 in broad panel melanoma cells. highly expressed metastatic and required tumor engraftment, growth, dissemination. Integrative genomics analyses reveal that transcriptional regulator controlling E2F/KLF-dependent cell-cycle DNA-repair genes. associates BRG1-containing remodeling complexes at promoters these silencing leads to decreased proliferation delayed DNA repair. Consequently, deficiency cooperates PARP inhibition induce death. Our study identifies as an gene demonstrates how its can be exploited target.