DNA methyltransferase 3B acts as a co-repressor of the human polycomb protein hPc2 to repress fibroblast growth factor receptor 3 transcription

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Kim, Sung-Hak; Park, Jinah; Choi, Moon-Chang; Park, Jung-Hyun; Kim, Hwang-Phill; Lee, Ju-Hee; Oh, Do-Youn; Im, Seock-Ah; Bang, Yung-Jue; Kim, Tae-You

Issue Date
Pergamon Press Ltd.
International Journal of Biochemistry and Cell Biology, Vol.40 No.11, pp.2462-2471
DNA methyltransferase 3B has been demonstrated to mediate gene silencing. The mechanisms how DNA methyltransferase 3B is targeted to specific regions and represses gene transcription, however, are not well understood. Here we show that by using yeast two-hybrid screening, DNA methyltransferase 3B interacts with the human polycomb protein, hPc2. This interaction was verified via co-immunoprecipitation and GST pull-down assay. Sequential deletion analysis showed that the region of DNA methyltransferase 3B responsible for interaction is mapped to the N-terminal regulatory domain. By performing a cDNA microarray analysis in HCr 116 cells, we identified that the expression of fibroblast growth factor receptor 3 is significantly increased upon the small interference RNA-mediated knockdown of hPc2, suggesting fibroblast growth factor receptor 3 as a potential target of hPc2. We further found that DNA methyltransferase 3B enhances hPc2-mediated transcriptional repression of fibroblast growth factor receptor 3, which does not require its de novo methyltransferase activity. Taken together, these results suggest that DNA methyltransferase 3B functions as a co-repressor of polycomb protein in inducing transcriptional repression independent of DNA methylation. (C) 2008 Elsevier Ltd. All rights reserved.
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College of Medicine/School of Medicine (의과대학/대학원)Dept. of Medicine (의학과)Journal Papers (저널논문_의학과)
Graduate School of Convergence Science and Technology (융합과학기술대학원)Dept. of Molecular and Biopharmaceutical Sciences (분자의학 및 바이오제약학과)Journal Papers (저널논문_분자의학 및 바이오제약학과)
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