KDM1 links nuclear GSK3β to epigenetic alterations
(CSCs) play an important role during the processes of tumor development, progression, and recurrence and are primarily responsible for therapeutic resistance and poor clinical outcome of patients (1). Epigenetic alterations, particularly histone methylation, have been increasingly recognized as a global transcriptional regulator that contributes to stem cell self-renewal and differentiation under physiological and pathological conditions (2). For example, methylations of Lys9 and Lys27 residues of histone H3 (H3K9me2/3 and H3K27me3), associate with heterochromatin and transcriptional repression; whereas H3K4me2/3, often found in active gene promoters, is associated with transcriptional activation. These epigenetic modiﬁcations create unique promoter architectures that control gene expression. Glycogen synthase kinase 3 beta (GSK3β) has been shown to take part in the regulation of histone methylation including H3K4 methylation in the promoter regions of multiple genes (3,4). However, the molecular mechanisms for GSK3β in mediating alterations of histone methylation remain to be defined. In September 2016 issue of Nature Cell Biology, Zhou et al. (5) addressed this challenge and singled out a connection between nuclear GSK3β and epigenetic aberration via regulation of lysine-specific histone demethylase 1A (KDM1A) stability.