title: Methylation-mediated regulation of E2F1 in DNA damage-induced cell death.
abstract: E2F1 promotes DNA damage-induced apoptosis and the post-translational modifications of E2F1 play an important role in the regulation of E2F1-mediated cell death. Here, we found that Set9 and LSD1 regulate E2F1-mediated apoptosis upon DNA damage. Set9 methylates E2F1 at lysine 185, a conserved residue in the DNA-binding domain of E2F family proteins. The methylation of E2F1 by Set9 leads to the stabilization of E2F1 and up-regulation of its proapoptotic target genes p73 and Bim, and thereby induces E2F1-mediated apoptosis in response to genotoxic agents. We also found that LSD1 demethylates E2F1 at lysine 185 and reduces E2F1-mediated cell death. The identification of the methylation/demethylation of E2F1 by Set9/LSD1 suggests that E2F1 is dynamically regulated by epigenetic enzymes in response to DNA damage.
authors.affiliation: Institute of Biophysics, Chinese Academy of Sciences, Beijing, China.
authors.forename: Qi
authors.initials: Q
authors.lastname: Xie
authors.forename: Yujie
authors.initials: Y
authors.lastname: Bai
authors.forename: Junbing
authors.initials: J
authors.lastname: Wu
authors.forename: Yu
authors.initials: Y
authors.lastname: Sun
authors.forename: Yadong
authors.initials: Y
authors.lastname: Wang
authors.forename: Ye
authors.initials: Y
authors.lastname: Zhang
authors.forename: Pinchao
authors.initials: P
authors.lastname: Mei
authors.forename: Zengqiang
authors.initials: Z
authors.lastname: Yuan
mesh_terms: D000595:Amino Acid Sequence; D016923:Cell Death / Q000187:drug effects; D002460:Cell Line; D004249:DNA Damage; D050687:E2F1 Transcription Factor / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D055785:Gene Knockdown Techniques; D056466:Histone Demethylases / Q000378:metabolism; D011495:Histone-Lysine N-Methyltransferase / Q000378:metabolism; D006801:Humans; D008239:Lysine / Q000378:metabolism; D008745:Methylation / Q000187:drug effects; D008969:Molecular Sequence Data; D055550:Protein Stability / Q000187:drug effects; D014158:Transcription, Genetic / Q000187:drug effects; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism
chemical_list: D050687:E2F1 Transcription Factor; C493753:E2F1 protein, human; D016159:Tumor Suppressor Protein p53; D056466:Histone Demethylases; C495195:KDM1A protein, human; D011495:Histone-Lysine N-Methyltransferase; C540312:SETD7 protein, human; D008239:Lysine