Expression of Twist2 is controlled by T-cell receptor signaling and determines the survival and death of thymocytes.

-Cacineurin-NFATc3 pathway, whereas strength of the TCR signal that results in negative selection abolishes NFATc3-dependent Twist2 induction via specific activation of the JNK pathway. Using Twist2-deficient and Twist2 transgenic mice, we also found that Twist2 determines thymocyte sensitivity to TCR-mediated apoptosis by regulating the expression of Nur77 and Nor-1. Twist2 partially retains histone deacetylase 7 (HDAC7) in the nucleus and recruits it to the Nur77 promoter region to repress Nur77 in positively selected thymocytes. Thus our results suggest a molecular mechanism of how thymocytes interpret the strength of the TCR signal and how TCR sensitivity is controlled during thymic selection.

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