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Targeting the Senescence-Overriding Cooperative Activity of Structurally Unrelated H3K9 Demethylases in Melanoma

Yu, Yong ; Schleich, Kolja ; Yue, Bin ; Ji, Sujuan ; Lohneis, Philipp ; Kemper, Kristel ; Silvis, Mark R. ; Qutob, Nouar ; van Rooijen, Ellen ; Werner-Klein, Melanie ; Li, Lianjie ; Dhawan, Dhriti ; Meierjohann, Svenja ; Reimann, Maurice ; Elkahloun, Abdel ; Treitschke, Steffi ; Dörken, Bernd ; Speck, Christian ; Mallette, Frédérick A. ; Zon, Leonard I. ; Holmen, Sheri L. ; Peeper, Daniel S. ; Samuels, Yardena ; Schmitt, Clemens A. ; Lee, Soyoung



Abstract

Oncogene-induced senescence, e.g., in melanocytic nevi, terminates the expansion of pre-malignant cells via transcriptional silencing of proliferation-related genes due to decoration of their promoters with repressive trimethylated histone H3 lysine 9 (H3K9) marks. We show here that structurally distinct H3K9-active demethylases-the lysine-specific demethylase-1 (LSD1) and several Jumonji C ...

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