biostudies-literatureOlney KCArizona Biomedical Research CommissionNational Cancer InstituteNCI NIH HHS83https://www.ebi.ac.uk/biostudies/studies/S-EPMC6156859biostudies-literatureUnknown12(1)<h4>Background</h4>Mounting evidence from genome-wide studies of cancer shows that chromatin-mediated epigenetic silencing at large cohorts of genes is strongly linked to a poor prognosis. This mechanism is thought to prevent cell differentiation and enable evasion of the immune system. Drugging the cancer epigenome with small molecule inhibitors to release silenced genes from the repressed state has emerged as a powerful approach for cancer research and drug development. Targets of these inhibitors include chromatin-modifying enzymes that can acquire drug-resistant mutations. In order to directly target a generally conserved feature, elevated trimethyl-lysine 27 on histone H3 (H3K27me3), we developed the Polycomb-based Transcription Factor (PcTF), a fusion activator that targets methyl-hiBMC systems biologyThe synthetic histone-binding regulator protein PcTF activates interferon genes in breast cancer cells.PMC6156859K01 CA18816414-082976Nyer DBHaynes KAOlney KCVargas DAWilson Sayres MAfalseThe synthetic histone-binding regulator protein PcTF activates interferon genes in breast cancer cells.<h4>Background</h4>Mounting evidence from genome-wide studies of cancer shows that chromatin-mediated epigenetic silencing at large cohorts of genes is strongly linked to a poor prognosis. This mechanism is thought to prevent cell differentiation and enable evasion of the immune system. Drugging the cancer epigenome with small molecule inhibitors to release silenced genes from the repressed state has emerged as a powerful approach for cancer research and drug development. Targets of these inhibitors include chromatin-modifying enzymes that can acquire drug-resistant mutations. In order to directly target a generally conserved feature, elevated trimethyl-lysine 27 on histone H3 (H3K27me3), we developed the Polycomb-based Transcription Factor (PcTF), a fusion activator that targets methyl-hi2018-01-01T00:00:00Z2018 Sep2026-05-01T19:46:35.542Z2019-03-26T23:57:32ZS-EPMC61568593025378110.1186/s12918-018-0608-4