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It monomethylates the transcription factor E2F1 (E2F transcription factor 1) and several other important proteins, but the functional consequences of many SETD6 mediated methylation events are unknown. In this study, the role of SETD6 mediated K117 monomethylation of E2F1 was investigated in prostate cancer cells. In chromatin binding and gene expression experiments, we identified distinct sets of genes that are bound and upregulated by methylated and unmethylated E2F1 indicating that E2F1 methylation by SETD6 directly modulates its chromatin interaction. In agreement with these findings, cellular data showed that E2F1 methylation affects oncogenic phenotypes. Mechanistically, we demonstrate with biochemical, cellular, and genomic assays that SETD6-mediated K117 methylation directly regulates the interaction of E2F1 and BRD4 by preventing K117 acetylation. Our data suggest that K117 methylation\/acetylation represents a switch controlling bromodomain binding to E2F1 by which SETD6 methylation regulates different cellular effects of E2F1. Similar mechanisms may apply to the regulation of other transcription factors by SETD6.<\/jats:p>","DOI":"10.1093\/nar\/gkaf1513","type":"journal-article","created":{"date-parts":[[2026,1,8]],"date-time":"2026-01-08T12:43:30Z","timestamp":1767876210000},"source":"Crossref","is-referenced-by-count":5,"title":["E2F1 K117 methylation by SETD6 disrupts BRD4\u2013E2F1 binding and modulates E2F1 chromatin binding and gene regulation in prostate cancer cells"],"prefix":"10.1093","volume":"54","author":[{"given":"Gizem Tugce","family":"Ulu","sequence":"first","affiliation":[{"name":"Institute of Biochemistry, University of Stuttgart , Allmandring 31, Stuttgart 70569 ,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Margarita","family":"Kublanovsky","sequence":"additional","affiliation":[{"name":"The Shraga Segal Department of Microbiology, Immunology and Genetics, Ben-Gurion University of the Negev , P.O.B. 653, Be\u2019er-Sheva 84105 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