To explore the effects of global alterations in histone methylation on the activation of the FA pathway, we exposed the transformed osteosarcoma cell line U2OS and the nontransformed telomerase (hTERT)-immortalized line BJ-TERT to the HMT inhibitors (HMTi) BRD4770 and BIX01294 and the HDM inhibitors (HDMi) GSK-J1 and PBIT, and examined FANCD2 and FANCI monoubiquitination. Here, FANCI is linked to osteosarcoma.