STAT3 can mediate epigenetic silencing of tumor suppressor genes (TSG). However, little is known about the molecular mechanisms involved, except that this action is mediated by DNA methylation and requires STAT3 acetylation. In this issue of Cancer Research, Gambi and colleagues confirm that oncogene-driven constitutive STAT3 acetylation is responsible for TSG silencing. Furthermore, they show that the Sin3a transcriptional repressor complex is an obligatory partner of STAT3 on the promoters of

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... the repressed genes, shedding light on the mechanisms involved in STAT3-mediated transcriptional repression, and more importantly, identifying that the STAT3-Sin3a axis is a potential selective therapeutic target in STAT3-dependent tumors.See related article by Gambi et al., p. 3076.