Super-enhancer-driven expression of BAHCC1 promotes melanoma cell proliferation and genome stability.
Fiche publication
Date publication
novembre 2023
Journal
Cell reports
Auteurs
Membres identifiés du Cancéropôle Est :
Dr COIN Frédéric, Dr DAVIDSON Irwin, Dr COMPE Emmanuel
Tous les auteurs :
Berico P, Nogaret M, Cigrang M, Lallement A, Vand-Rajabpour F, Flores-Yanke A, Gambi G, Davidson G, Seno L, Obid J, Vokshi BH, Le Gras S, Mengus G, Ye T, Cordero CF, Dalmasso M, Compe E, Bertolotto C, Hernando E, Davidson I, Coin F
Lien Pubmed
Résumé
Super-enhancers (SEs) are stretches of enhancers ensuring a high level of expression of key genes associated with cell function. The identification of cancer-specific SE-driven genes is a powerful means for the development of innovative therapeutic strategies. Here, we identify a MITF/SOX10/TFIIH-dependent SE promoting the expression of BAHCC1 in a broad panel of melanoma cells. BAHCC1 is highly expressed in metastatic melanoma and is required for tumor engraftment, growth, and dissemination. Integrative genomics analyses reveal that BAHCC1 is a transcriptional regulator controlling expression of E2F/KLF-dependent cell-cycle and DNA-repair genes. BAHCC1 associates with BRG1-containing remodeling complexes at the promoters of these genes. BAHCC1 silencing leads to decreased cell proliferation and delayed DNA repair. Consequently, BAHCC1 deficiency cooperates with PARP inhibition to induce melanoma cell death. Our study identifies BAHCC1 as an SE-driven gene expressed in melanoma and demonstrates how its inhibition can be exploited as a therapeutic target.
Mots clés
BAHCC1, CP: Cancer, gene expression, genome stability, melanoma, super-enhancer
Référence
Cell Rep. 2023 11 2;42(11):113363