Thymocytes undergo massive proliferation before T cell receptor (TCR) gene 
rearrangement, ensuring the diversification of the TCR repertoire. Because 
activated cells are more susceptible to damage, cell-death restraint as well as 
promotion of cell-cycle progression is considered important for adequate cell 
growth. Although the molecular mechanism of pre-TCR-induced proliferation has 
been examined, the mechanisms of protection against cell death during the 
proliferation phase remain unknown. Here we show that the survival of activated 
pre-T cells induced by pre-TCR signaling required the Polycomb group (PcG) gene 
product Bmi-1-mediated repression of Cdkn2A, and that p19Arf expression resulted 
in thymocyte cell death and inhibited the transition from CD4(-)CD8(-) (DN) to 
CD4(+)CD8(+) (DP) stage upstream of the transcriptional factor p53 pathway. The 
expression of Cdkn2A (the gene encoding p19Arf) in immature thymocytes was 
directly regulated by PcG complex containing Bmi-1 and M33 through the 
maintenance of local trimethylated histone H3K27. Our results indicate that this 
epigenetic regulation critically contributes to the survival of the activated 
pre-T cells, thereby supporting their proliferation during the DN-DP transition.