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Despite the identification of the epigenetical silencing of the <jats:italic>NY\u2010ESO1<\/jats:italic> gene in a large variety of tumors, the molecular mechanism involved in this phenomenon is not fully elucidated. In two non epithelial cancers (glioma and mesothelioma), we found that the epigenetic regulation of the <jats:italic>NY\u2010ESO1<\/jats:italic> gene requires the sequential recruitment of the HDAC1\u2010mSin3a\u2010NCOR, Dnmt3b\u2010HDAC1\u2010Egr1 and Dnmt1\u2010PCNA\u2010UHRF1\u2010G9a complexes. 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