Bmii regulates memory Th cell survival via repression of the Noxa gene

摘要

The Polycomb group (PcG) gene Bmi1 has recently been implicated in the maintenance of hematopoietic, neural and cancer stem cells. We herein demonstrate that Bmil plays a crucial role in the generation and maintenance of memory T helper (Th) cells. In the absence of Bmil, the generation of Th1/Th2 memory cells was impaired by the increased frequency of apoptotic cell death. Bmil binds to the proapoptotic BH3-only protein Noxa gene locus, and directly represses its transcription, thus supporting the survival of memory Thl/Th2 cells. We also demonstrate the involvement of H3-K27 tri-methylation and DNA CpG methylation in the repression of the Noxa gene. Furthermore, the generation of memory Th cells was restored by the deletion of Noxa but not Ink4a and Arf. Thus, Bmil is considered to control memory Th cell survival through the direct repression of the Noxa gene.