
ALT Schematic representation of KDM6B safeguarding tissue homeostasis to mechanical stress through epigenetic control of PIEZO1- mediated mechanotransduction. Using the mouse incisor as a model of mechanical loading, we reveal that within TACs, Kdm6b demethylates H3K27me3, thereby relieving the repression of the Bmi1 gene. Normal BMI1 inhibits Piezo1 expression. This maintains physiological PIEZO1 levels, ensuring calibrated Ca2+ influx for proliferation and differentiation. In contrast, loss of Kdm6b leads to an accumulation of H3K27me3 at the Bmi1 promoter region, which silences Bmi1 expression and diminishes BMI1 formation. This reduction results in pathologically increased PIEZO1 ion channels in the membrane. The subsequent Ca2+ overload triggers TAC apoptosis while reducing proliferation and differentiation. Ultimately, these molecular events compromise tissue homeostasis. Schematic created with BioRender.com. Ho, T. (2026) https://BioRender.com/8mzv4a














