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Therapeutic interventions that simultaneously target opposing arms of bistable switches can reinstate proper dynamics without permanently biasing the system towards either state. Conditional deletion of lysine-specific histone demethylase 1A in adult mouse neurons provided mechanistic evidence for this principle, as the resulting accumulation of monomethylated and trimethylated histone H3 Lys4 (H3K4me1/3) blocked the recruitment of Polycomb repressive complex 2 (PRC2) and led to H3K27me3 loss69. Recent systematic screens for rejuvenating transcription factors have identified EZH2 overexpression as particularly effective at reprogramming late-passage cells back to younger gene expression states while improving cell division, reducing senescence and enhancing mitochondrial function, thereby providing direct evidence for the therapeutic potential of targeting PRC2 catalytic activity151.