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    請使用永久網址來引用或連結此文件: http://ir.lib.ncu.edu.tw/handle/987654321/51081


    題名: A chemical probe selectively inhibits G9a and GLP methyltransferase activity in cells
    作者: Vedadi,M;Barsyte-Lovejoy,D;Liu,F;Rival-Gervier,S;Allali-Hassani,A;Labrie,V;Wigle,TJ;DiMaggio,PA;Wasney,GA;Siarheyeva,A;Dong,AP;Tempel,W;Wang,SC;Chen,X;Chau,I;Mangano,TJ;Huang,XP;Simpson,CD;Pattenden,SG;Norris,JL;Kireev,DB;Tripathy,A;Edwards,A;Roth,BL;Janzen,WP;Garcia,BA;Petronis,A;Ellis,J;Brown,PJ;Frye,SV;Arrowsmith,CH;Jin,J
    貢獻者: 系統生物與生物資訊研究所
    關鍵詞: PLURIPOTENT STEM-CELLS;HISTONE METHYLTRANSFERASES;DNA METHYLATION;LYSINE-9 METHYLATION;CHROMATIN-STRUCTURE;CANCER-CELLS;P53;TRANSCRIPTION;REPRESSION;COMPLEXES
    日期: 2011
    上傳時間: 2012-03-27 18:20:52 (UTC+8)
    出版者: 國立中央大學
    摘要: Protein lysine methyltransferases G9a and GLP modulate the transcriptional repression of a variety of genes via dimethylation of Lys9 on histone H3 (H3K9me2) as well as dimethylation of non-histone targets. Here we report the discovery of UNC0638, an inhibitor of G9a and GLP with excellent potency and selectivity over a wide range of epigenetic and non-epigenetic targets. UNC0638 treatment of a variety of cell lines resulted in lower global H3K9me2 levels, equivalent to levels observed for small hairpin RNA knockdown of G9a and GLP with the functional potency of UNC0638 being well separated from its toxicity. UNC0638 markedly reduced the clonogenicity of MCF7 cells, reduced the abundance of H3K9me2 marks at promoters of known G9a-regulated endogenous genes and disproportionately affected several genomic loci encoding microRNAs. In mouse embryonic stem cells, UNC0638 reactivated G9a-silenced genes and a retroviral reporter gene in a concentration-dependent manner without promoting differentiation.
    關聯: NATURE CHEMICAL BIOLOGY
    顯示於類別:[系統生物與生物資訊研究所] 期刊論文

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