New publication in "Nucleic Acids Research"

New publication in "Nucleic Acids Research"

The SETD6 protein methyltransferase monomethylates the transcription factor E2F1 specifically at lysine 117. Together with our cooperation partner Prof. Dr. Dan Levy at Ben-Gurion University of the Negev in Israel, we investigated chromatin binding and gene regulation by methylated and unmethylated E2F1 and identified group of differentially regulated genes many of them connected to cancer related phenotypes. In agreement with this, the depletion of SETD6 in SETD6 KO cells revealed reduced apoptosis and enhanced cell proliferation. Hence, our data indicate that SETD6 mediated K117 methylation leads to a switch in the transcriptional role of E2F1. Mechanistically, the methylation of K117 prevents acetylation at this site, thereby inhibiting the interaction of E2F1 with BRD4. In a more general context, our data suggest that K117 methylation/acetylation of E2F1 may represent an important methyl/acetyl switch leading to a wide range of potential cellular effects triggered by monomethylation of a single lysine residue.