Skip to main content
. 2012 Apr;32(8):1433–1441. doi: 10.1128/MCB.06315-11

Fig 6.

Fig 6

A model for Twist-1 regulation of the Ink4A/Arf locus. In this model, early-passage BMSCs have high levels of Twist-1, which normally increases the levels of EZH2 and recruitment to the p14, p16 transcription start site (TSS). This corresponds to increased levels of H3K27me3 along the Ink4A/Arf locus, leading to repression. Twist-1 also reduces the levels of E47 and binds the p16 promoter, aiding in repression. As the cells senesce, the levels of Twist-1 decrease, leading to a reduction in H3K27me3 along the Ink4A/Arf locus. This coincides with an increase in E47, resulting in transcriptional activation of p14/p16. When Twist-1 is overexpressed, this results in increased EZH2 and reduced E47, which represses the Ink4A/Arf locus, hence repressing senescence and increasing the life span of BMSCs.