Inhibition of the RAS-ERK pathway promotes the recruitment of the HDAC1 repressor complex to mutant TERT promoters of melanoma cells. (A) HDAC1 and Sp1 ChIP was performed in the BRAF-mutant, TERT promoter mutant melanoma cells WM793, UACC257, Malme-3M, and A375, which were treated either with si-BRAF or BRAF and MEK inhibitors to disrupt ERK activation. Enrichment of TERT promoter DNA fragments in ChIP DNA was normalized to DNA input. Data shown are representative of two independent experiments. *P < 0.05; Student’s t test (two-tailed). (B) A model for TERT reactivation at mutant TERT promoter during constitutive RAS-ERK signaling in BRAF-mutant melanoma tumors is shown.