Essay Example on Transcriptional regulation of Arf Transcriptional Control

The polycomb group gene Bmi1 suppresses cellular senescence through repression of Arf transcription 58 Bmi1 deficient MEFs shows decreased cell cycle progression and increased premature senescence which are rescued by Arf Ink4a depletion 59 Bmi1 also requires the EZH2 containing Polycomb Repressive Complex 2 PRC2 to repress ARF INK4a transcription PRC2 maintains the levels of H3K27Me3 as well as the Bmi1 PRC1 complex at the locus The polycomb group gene CBX7 increases the lifespan of normal human cells and MEFs through suppression of Arf Ink4a expression independent of Bmi1 60 TBX2 immortalizes MEFs and decreases senescence in normal human cells by repression of Arf transcription 61 Fig 2 The basic helix loop helix transcription factor Twist1 activates the recruitment of EZH2 to the Arf transcription start site Thus it increases the levels of H3K27Me3 on the ARF INK4a locus followed by repression of Arf transcription 62 63 In general the relative importance of the Arf gene far exceeds that of p16Ink4a in repression of the Arf Ink4a locus in mice reflecting the strong tumor prone tendency of Arf deficient mice 7 64 than p16Ink4a deficient mice 8 9 leaving an open question in human cases since in vivo assays are not possible in the latter