5-Methylation of cytosine residues in DNA is a heritable epigenetic mark that regulates gene expression. DNA methyltransferases (DNA MTase, (DNMTs)) catalyze the transfer of the CH3 group from S?adenosylmethionine (AdoMet) to DNA (Melanie E & Lacey M 2014; Laisne M et al. 2018). DNMTs associate with EZH2 of the Polycomb Repressive Complex 2 (PRC2) (Vire et al. 2006). Aberrant promoter methylation is considered to be a hallmark of cancer (Ehrlich M et al. 2002; Dong Y et al. 2014; Lam K et al. 2016; Croes L et al. 2018). Epigenetic inactivation of GSDME due to hypermethylation of the GSDME promoter region has been linked to tumorigenesis (Akino K et al. 2007; Kim MS et al. 2008a,b; Croes L et al. 2017, 2018; Ibrahim J et al. 2019). Treatment with the DNA methyltransferase inhibitors such as FDA?approved decitabine (5?aza?2'?deoxycytidine or DAC) may elevate GSDME expression in certain cancer cells (Akino K et al. 2007; Fujikane T et al. 2009; Wang Y et al. 2017).
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